一个扩展的相互作用位点决定了网格蛋白介导的内吞作用中AP180和AP2之间的结合-动脉网

An extended interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis

Nature 等信源发布 2024-07-13 17:08

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AbstractThe early phases of clathrin mediated endocytosis are organized through a highly complex interaction network mediated by clathrin associated sorting proteins (CLASPs) that comprise long intrinsically disordered regions (IDRs). AP180 is a CLASP exclusively expressed in neurons and comprises a long IDR of around 600 residues, whose function remains partially elusive.

摘要网格蛋白介导的内吞作用的早期阶段是通过网格蛋白相关分选蛋白（CLASP）介导的高度复杂的相互作用网络组织的，该网络包含长的内在无序区域（IDR）。AP180是仅在神经元中表达的CLASP，包含约600个残基的长IDR，其功能仍然部分难以捉摸。

Using NMR spectroscopy, we discovered an extended and strong interaction site within AP180 with the major adaptor protein AP2, and describe its binding dynamics at atomic resolution. We find that the 70 residue-long site determines the overall interaction between AP180 and AP2 in a dynamic equilibrium between its bound and unbound states, while weaker binding sites contribute to the overall affinity at much higher concentrations of AP2.

。我们发现，70个残基长的位点决定了AP180和AP2之间在其结合态和未结合态之间的动态平衡中的整体相互作用，而较弱的结合位点在更高浓度的AP2下有助于整体亲和力。

Our data suggest that this particular interaction site might play a central role in recruitment of adaptors to the clathrin coated pit, whereas more transient and promiscuous interactions allow reshaping of the interaction network until cargo uptake inside a coated vesicle..

我们的数据表明，这个特定的相互作用位点可能在将衔接子募集到网格蛋白包被的凹坑中起着核心作用，而更短暂和混杂的相互作用则允许重塑相互作用网络，直到在包被的囊泡内吸收货物。。

IntroductionClathrin Mediated Endocytosis (CME) is the most widespread form of endocytosis1, leading to the formation of small vesicles (from around 20 to 60 nanometers in diameter2) that transport cargo proteins into the cytoplasm. It is key to many cellular processes such as nutrient absorption, membrane composition regulation, signaling, adhesion, and viral entryway into the cell.

引言网格蛋白介导的内吞作用（CME）是最广泛的内吞作用形式1，导致形成小囊泡（直径约20至60纳米2），将货物蛋白运输到细胞质中。它是许多细胞过程的关键，例如营养吸收，膜组成调节，信号传导，粘附和病毒进入细胞。

A lattice formed by a number of clathrin triskelia builds the exoskeleton of the clathrin-coated vesicles. Clathrin itself, however, cannot bind to the membrane or the incorporated cargo and requires a complex network of adapter and accessory proteins to enable controlled cargo uptake3. The major adapter complex AP2, composed of four different subunits, recognizes cargo, as well as the signaling lipid phosphatidylinositol-(4,5)-bisphosphate (PIP2), and is recognized by clathrin.

由许多网格蛋白triskelia形成的晶格构建了网格蛋白包被的囊泡的外骨骼。然而，网格蛋白本身不能与膜或掺入的货物结合，需要复杂的衔接子和辅助蛋白网络才能控制货物摄取3。主要的衔接子复合物AP2由四个不同的亚基组成，可识别货物以及信号脂质磷脂酰肌醇-（4,5）-二磷酸（PIP2），并被网格蛋白识别。

Its α and β2 subunits, the two largest subunits, form the core of the AP2 complex and comprise two intrinsically disordered linkers followed by C-terminal appendage domains4. The appendage domains and linkers are known to bind clathrin and possess binding pockets for accessory proteins, also called clathrin associated sorting proteins (CLASPs)5,6.

它的α和β2亚基（两个最大的亚基）形成AP2复合物的核心，并包含两个本质上无序的接头，然后是C端附属物结构域4。已知附属物结构域和接头结合网格蛋白并具有辅助蛋白的结合口袋，也称为网格蛋白相关分选蛋白（CLASP）5,6。

CLASPs are usually composed of an N-terminal folded domain, which binds the membrane and can often recognize certain cargoes, and a large C-terminal intrinsically disordered domain, comprising small linear motifs (SLiMs) that interact with the AP2 appendage domain, the clathrin terminal domain, or folded domains of other CLASPs7,8.

CLASP通常由一个结合膜并通常可以识别某些货物的N端折叠结构域和一个大的C端固有无序结构域组成，该结构域包含与AP2附属物结构域相互作用的小线性基序（SLIM），网格蛋白末端结构域或其他CLASP的折叠结构域7,8。

Amongst those count, for example, proteins that take part in the pioneering module, such as the F-BAR domain-only protein 1 and 2 (FCHO1/2), the clathrin assembly lymphoid myeloid leukemia (CALM) protein, or the Epidermal growth factor substrate.

例如，其中包括参与开创性模块的蛋白质，例如仅F-BAR结构域的蛋白质1和2（FCHO1/2），网格蛋白组装的淋巴样髓性白血病（CALM）蛋白质或表皮生长因子底物。

While AP180 is recognized for enhancing clathrin assembly, synergy with AP2 for its assembly function has been proposed16 and the α-appendage domain of AP2 has been shown to pull down AP18026. We have thus analyzed the binding between AP180 and the α-appendage domain of AP2 (from now on called AP2α).

虽然AP180被认为可以增强网格蛋白的组装，但已经提出了与AP2的组装功能协同作用16，并且AP2的α-附件结构域已被证明可以拉下AP18026。因此，我们分析了AP180与AP2的α-附肢结构域（从现在起称为AP2α）之间的结合。

We employed a similar approach to our investigation of the binding of AP180 and CHCTD, and titrated increasing concentrations of AP2α into AP180IDR and the different AP180 segments. Even though only two putative binding sites for AP2α are contained in the entire length of the AP180 IDR (around residues 400 and 480), we observe interactions, accompanied by increased 15N R1ρ relaxation rates, at various positions along the chain of AP180 (Fig. 3, Supplementary Fig. 11).

。尽管在AP180 IDR的整个长度（残基400和480附近）中仅包含两个AP2α的推定结合位点，但我们观察到在AP180链的各个位置上的相互作用，伴随着15N R1ρ弛豫率的增加（图3，补充图11）。

Binding between AP180 and AP2α thus seems to be remarkably promiscuous, with classical clathrin binding motifs DLL/DLF binding with apparently equal strength as DPF motifs or FxDxF, normally known to bind the AP2 α- and β2 appendage domains. A thorough analysis of AP180 15N R1ρ rates reveals that not only DLL/DLF, DPF and FxDxF motifs engage in binding, but that AP2α seems to interact with small hydrophobic clusters within the sequence of AP180 in a very general sense (Supplementary Fig. 11).

因此，AP180和AP2α之间的结合似乎是非常混杂的，经典的网格蛋白结合基序DLL/DLF的结合强度显然与DPF基序或FxDxF相同，通常已知它们结合AP2α和β2附件结构域。对AP180 15N R1ρ率的彻底分析表明，不仅DLL/DLF，DPF和FxDxF基序参与结合，而且AP2α似乎在非常普遍的意义上与AP180序列内的小疏水簇相互作用（补充图11）。

Intriguingly, the very C-terminal stretch of AP180, encompassed in the AP180720–898 segment, is devoid of known binding motifs but contains hydrophobic residues, and yet does not show any sign of interaction with AP2α. In order to assess the binding strengths of AP2α to the individual motifs within AP180, we undertook an analysis of the measured relaxation rates of AP180 at different admixtures of AP2α, which revealed equilibrium dissociation constants that are overall comparable to those observed for CHCTD binding (hundr.

有趣的是，包含在AP180720-898片段中的AP180的C末端片段没有已知的结合基序，但包含疏水残基，但没有与AP2α相互作用的迹象。。

The length of the EIM, as well as the comparably high affinity of this interaction site poses the question as to how it would bind to the surface of AP2β2. Both AP2α and AP2β2 are known to harbor binding sites for SLiMs contained in CLASPs, which have been mapped using crystallography and pull-down experiments5,6,17,28,29.

EIM的长度以及该相互作用位点相对较高的亲和力提出了一个问题，即它如何与AP2β2的表面结合。已知AP2α和AP2β2都含有卡环中所含粘液的结合位点，这些位点已使用晶体学和下拉实验进行了定位5,6,17,28,29。

Two such sites exist per appendage domain, one in the platform domain (C-terminal part of the appendage domain) and one in the sandwich domain (N-terminal part of the appendage domain) for AP2α as well as AP2β2, both able to independently bind the described linear motifs. Mutants of AP2β2 have been described to either alter (K842E, Y888E) or totally disrupt (Y815A) pull-down of AP180 by the GST-tagged AP2 β2-appendage domain6.

每个附属物结构域存在两个这样的位点，一个位于平台结构域（附属物结构域的C端部分），另一个位于夹心结构域（附属物结构域的N端部分），用于AP2α和AP2β2，两者都能够独立地结合所描述的线性基序。已经描述了AP2β2的突变体通过GST标记的AP2β2-附件结构域6改变（K842E，Y888E）或完全破坏（Y815A）AP180的下拉。

K842 and Y888 reside on the C-terminal platform domain and Y815 on the N-terminal sandwich domain of the β2-appendage domain.We assessed binding of AP180399–598 to the AP2β2 mutants described (K842E, Y888E, Y815E) and measured 15N spin relaxation (R1ρ) of AP180399–598 at 50% and 100% excess of wild type and mutant AP2β2.

K842和Y888位于C端平台结构域上，Y815位于β2-附肢结构域的N端三明治结构域上。我们评估了AP180399-598与所述AP2β2突变体（K842E，Y888E，Y815E）的结合，并测量了野生型和突变型AP2β2过量50%和100%时AP180399-598的15N自旋弛豫（R1ρ）。

Strikingly, binding of AP180399–598 to AP2β2 persists for all mutants. This becomes obvious when focusing on the peaks within the EIM, which totally disappear at an excess of 50% wild-type AP2β2. In the presence of 50% AP2β2 mutants the respective peaks significantly broaden (and show increased 15N R1ρ rates), albeit not to disappearance, demonstrating that the interaction persists, but is weakened (Fig. 6).

引人注目的是，对于所有突变体，AP180399-598与AP2β2的结合都持续存在。当关注EIM内的峰时，这一点变得很明显，这些峰在超过50%的野生型AP2β2时完全消失。。

This suggests that both platform and sandwich domains may be simultaneously bound by AP180’s EIM, as none of the mutations abolishes, but all affect binding. Interestingly, the two DLF/FxDxF motifs towards the C-terminus of AP180399-598 (DIFGDLFD, 562–569/DLFGTDAF, 587–594) seem to bind more strongly to all .

这表明平台和三明治结构域都可能同时被AP180的EIM结合，因为没有突变被消除，但都会影响结合。。

15N relaxation, relaxation dispersion, and titrationsUtilizing the procedures detailed in the main text and figures, we investigated the interactions involving AP180 and its associated partners. Extraction of peak intensities (I) and 1H, as well as 15N chemical shifts, was carried out from 1H-15N HSQC or 1H-15N TROSY (AP2β2) spectra.

15N弛豫，弛豫色散和滴定利用正文和图中详述的程序，我们研究了涉及AP180及其相关伙伴的相互作用。从1H-15N HSQC或1H-15N TROSY（AP2β2）光谱中提取峰强度（I）和1H以及15N化学位移。

Combined chemical shift perturbations (CSPs) were calculated using$${CSP}=\sqrt{{\left(\delta ^{1}H \cdot 6.5\right)}^{2}+{\left(\delta ^{15}N \right)}^{2}}$$.

使用$${CSP}=\ sqrt{{\ left（\ delta）计算组合化学位移扰动（CSP）^{1}H\cdot 6.5 \右）}^{2}+{\左（\ delta^{15}N\右）}^{2}}$$。

(1)

Titration of the different AP180 segments with CHCTD was performed by titrating unlabeled CHCTD in 50 mM Na-phosphate pH 7.5, 150 mM NaCl, and 2 mM dithiothreitol (DTT) into 15N labeled AP180 in NMR buffer (pH 6). Control experiments were performed through titrating the same amount of pH 7.5 buffer into AP180 segments to exclude CSPs through altered buffer conditions.All other proteins were in NMR buffer and no particular caution had to be taken in the titration experiments.15N R1ρ relaxation rates53 were assessed at 600, 750 MHz and 900 MHz, maintaining a concentration of 100 μM of [U-15N]-labeled or [U-15N, U-13C]-labeled AP180 (IDR or segments) unless otherwise noted, and with varying amounts of partner, as outlined in the figures.

通过将未标记的CHCTD在50mM磷酸钠pH 7.5150mM NaCl和2mM二硫苏糖醇（DTT）中滴定到NMR缓冲液（pH 6）中的15N标记的AP180中，用CHCTD滴定不同的AP180片段。通过将相同量的pH 7.5缓冲液滴定到AP180片段中进行对照实验，以通过改变缓冲液条件排除CSP。所有其他蛋白质都在NMR缓冲液中，在滴定实验中不必特别小心.15N R1ρ弛豫率53在600750MHz和900MHz下进行评估，保持浓度为100μM的[U-15N]标记或[U-15N，U-13C]标记的AP180（IDR或片段），除非另有说明，并且具有不同量的伴侣，如图所示。

The spin-lock field was set to 1500 Hz, and 7 delays, between 10 and 230 ms, were used to sample the decay of magnetization. Error bars were estimated from Monte Carlo simulations of the experimental uncertainty.For fast exchange behavior between the unbound and bound AP180, residue specific KD values were approximated from the measured 15N R1ρ relaxation rates.

将自旋锁定场设置为1500 Hz，并使用10至230 ms之间的7个延迟来采样磁化的衰减。通过实验不确定性的蒙特卡罗模拟估计误差棒。对于未结合和结合的AP180之间的快速交换行为，残基特异性KD值由测得的15N R1ρ弛豫率近似。

At a spin-lock field of 1500 Hz and only small changes in R1 throughout the titration, the following relation can be approximated under the condition of weak binding25,54:$${R}_{1\rho }=\frac{\left[{B}_{{tot}}\right]}{{K}_{D}+\left[{A}_{{tot}}\right]}\left({R}_{1\rho }^{B}-{R}_{1\rho }^{A}\right)+{R}_{1\rho }^{A}.$$.

在1500 Hz的自旋锁定场下，整个滴定过程中R1只有很小的变化，在弱结合条件下可以近似以下关系25,54：$${R}_{1\rho}=\frac{\left[{B}_{{{tot}}\右]}{{K}_{D} +\左[{A}_{{{tot}}\右]}\左({R}_{1\rho}^{B}-{R}_{1\rho}^{A}\右）+{R}_{1\rho}^{A}.$$。

(2)

We measured R1ρB of the respective binding partners. The residue-wise KD value can then be obtained from a linear fit of AP180 15N R1ρ rates plotted against the concentration of added interaction partner (CHCTD or AP2α).Relaxation dispersion experiments were conducted at 600 and 850 MHz, employing 14 CPMG frequencies ranging from 31 to 1000 Hz, with a constant-time relaxation of 32 ms.

我们测量了各个结合伴侣的R1ρB。然后可以从AP180 15N R1ρ速率与添加的相互作用伴侣（CHCTD或AP2α）浓度的线性拟合中获得残基KD值。弛豫色散实验在600和850 MHz下进行，采用14个CPMG频率，范围从31到1000 Hz，恒定时间弛豫为32 ms。

Errors were determined based on standard deviations of repeat measurements. The minimum error was set to 0.5. This was carried out on 100 μM 15N AP180399–598 with 10 μM unlabeled AP2β2. Data encompassing all 22 non-overlapped residues showing dispersion were collectively fitted using ChemEx (https://github.com/gbouvignies/chemex) using a two-state exchange model.

根据重复测量的标准偏差确定误差。最小误差设置为0.5。这是在100μM15N AP180399-598和10μM未标记的AP2β2上进行的。使用ChemEx对包含所有22个显示分散的非重叠残基的数据进行了集体拟合(https://github.com/gbouvignies/chemex)使用两态交换模型。

The population of AP180 bound to AP2β2 (pB) and the exchange rate (kex) were derived from the fitting. The KD value was calculated from the concentrations of both proteins used in the CPMG experiment and pB under the assumption of a 1:1 binding stoichiometry.For cloning reasons, plots of NMR parameters along the sequence of AP180 are shifted by +1 compared to the sequence of the full length AP180.Isothermal titration calorimetryBinding of AP180 to AP2β2 was investigated by Isothermal Titration Calorimetry on a iMicroCal iTC200 from Malvern at 25 °C.

通过拟合得出与AP2β2（pB）结合的AP180种群和汇率（kex）。在1:1结合化学计量的假设下，根据CPMG实验中使用的两种蛋白质和pB的浓度计算KD值。由于克隆原因，与全长AP180的序列相比，沿着AP180序列的NMR参数图偏移了+1。等温滴定量热法通过等温滴定量热法在Malvern的亚微米iTC200上研究了AP180与AP2β2的结合。25°C。

The experiments were conducted on 0.03 mM AP180IDR, AP180399–598, and AP180430–500 in the microcalorimeter cell, adding 2 μl of AP2β2 (0.3 mM) at each titration step. The buffer was 150 mM NaCl, 50 mM Na-phosphate, and 0.2 mM TCEP (pH 7.5). Titration of 0.3 mM AP2β2 into buffer was recorded as a negative control and showed a flat curve.

实验在微量量热池中的0.03 mM AP180IDR，AP180399-598和AP180430-500上进行，在每个滴定步骤中加入2μlAP2β2（0.3 mM）。缓冲液为150 mM NaCl，50 mM磷酸钠和0.2 mM TCEP（pH 7.5）。记录将0.3mM AP2β2滴定到缓冲液中作为阴性对照，并显示平坦曲线。

For binding of AP180399–598 to AP2β2 mutants, 0.04 mM AP180399–598 was kept in the microcalorimeter cell. The titration curves were fi.

为了将AP180399-598与AP2β2突变体结合，将0.04mM AP180399-598保存在微量热量计细胞中。滴定曲线为fi。

Data availability

数据可用性

Data supporting the findings of this paper are available from the corresponding author upon request and can be found in the Source Data file. Cross-link MS data generated in this study have been deposited on proteomeXchange under the accession code PXD049300. NMR assignments generated in this study have been deposited in the Biological Magnetic Resonance Bank under accession numbers 52320 (AP2β2), 52322 (AP180281-500), 52323 (AP180399-598), 52324 (AP180471-700), 52325 (AP180540-740), and 52326 (AP180720-898).The PDB entry of AP2β2 used in this work is: 1E42 (Beta2-adaptin appendage domain, from clathrin adapter AP2). Source data are provided with this paper..

支持本文研究结果的数据可应要求从通讯作者处获得，并可以在源数据文件中找到。本研究中产生的交联MS数据已保存在proteomeXchange上，登录号为PXD049300。本研究中产生的NMR分配已保存在生物磁共振库中，登录号为52320（AP2β2），52322（AP180281-500），52323（AP180399-598），52324（AP180471-700），52325（AP180540-740）和52326（AP180720-898）。这项工作中使用的AP2β2的PDB条目是：1E42（来自网格蛋白适配器AP2的Beta2 adaptin appendage域）。本文提供了源数据。。

ReferencesBitsikas, V., Corrêa, I. R. Jr & Nichols, B. J. Clathrin-independent pathways do not contribute significantly to endocytic flux. eLife 3, e03970 (2014).Article

参考文献Bitsikas，V.，Corrêa，I.R.Jr＆Nichols，B.J。网格蛋白非依赖性途径对内吞通量没有显着贡献。eLife 3，e03970（2014）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Paraan, M. et al. The structures of natively assembled clathrin-coated vesicles. Sci. Adv. 6, eaba8397 (2020).Article

Paraan，M.等人。天然组装的网格蛋白包被囊泡的结构。科学。Adv.6，eaba8397（2020）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Taylor, M. J., Perrais, D. & Merrifield, C. J. A High Precision Survey of the Molecular Dynamics of Mammalian Clathrin-Mediated Endocytosis. PLOS Biol. 9, e1000604 (2011).Article

Taylor，M.J.，Perrais，D。和Merrifield，C.J。哺乳动物网格蛋白介导的内吞作用的分子动力学的高精度调查。《公共科学图书馆·生物学》。9，e1000604（2011）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Collins, B. M., McCoy, A. J., Kent, H. M., Evans, P. R. & Owen, D. J. Molecular Architecture and Functional Model of the Endocytic AP2 Complex. Cell 109, 523–535 (2002).Article

Collins，B.M.，McCoy，A.J.，Kent，H.M.，Evans，P.R。＆Owen，D.J。内吞AP2复合物的分子结构和功能模型。细胞109523-535（2002）。文章

PubMed

Google Scholar

谷歌学者

Praefcke, G. J. K. et al. Evolving nature of the AP2 alpha-appendage hub during clathrin-coated vesicle endocytosis. EMBO J. 23, 4371–4383 (2004).Article

Praefcke，G.J.K.等人。网格蛋白包被的囊泡内吞过程中AP2α附属物中枢的进化性质。EMBO J.234371–4383（2004）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schmid, E. M. et al. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 4, e262 (2006).Article

Schmid，E.M.等人。AP2β附属物中心在招募网格蛋白包被的囊泡组装伙伴中的作用。。4，e262（2006）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Maldonado-Báez, L. & Wendland, B. Endocytic adaptors: recruiters, coordinators and regulators. Trends Cell Biol. 16, 505–513 (2006).Article

Maldonado-Báez，L。＆Wendland，B。内吞适配器：招聘人员，协调员和监管人员。趋势细胞生物学。。文章

PubMed

Google Scholar

谷歌学者

Takei, K. & Haucke, V. Clathrin-mediated endocytosis: membrane factors pull the trigger. Trends Cell Biol. 11, 385–391 (2001).Article

Takei，K。＆Haucke，V。网格蛋白介导的内吞作用：膜因子触发。趋势细胞生物学。11385-391（2001）。文章

PubMed

Google Scholar

谷歌学者

Kaksonen, M. & Roux, A. Mechanisms of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 19, 313–326 (2018).Article

Kaksonen，M。＆Roux，A。网格蛋白介导的内吞作用的机制。Nat。Rev。Mol。Cell Biol。。文章

PubMed

Google Scholar

谷歌学者

Ford, M. G. J. et al. Simultaneous Binding of PtdIns(4,5)P2 and Clathrin by AP180 in the Nucleation of Clathrin Lattices on Membranes. Science 291, 1051–1055 (2001).Article

Ford，M.G.J.等人。在膜上网格蛋白晶格的成核过程中，AP180同时结合PtdIns（4,5）P2和网格蛋白。科学2911051-1055（2001）。文章

ADS

PubMed

Google Scholar

谷歌学者

Koo, S. J. et al. SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses. Proc. Natl Acad. Sci. USA 108, 13540–13545 (2011).Article

Koo，S.J.等人。SNARE基序通过内吞衔接子网格蛋白组装淋巴样骨髓性白血病（CALM）和突触处的AP180介导突触短纤维蛋白的分选。程序。国家科学院。科学。美国10813540–13545（2011）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Maritzen, T., Koo, S. J. & Haucke, V. Turning CALM into excitement: AP180 and CALM in endocytosis and disease. Biol. Cell 104, 588–602 (2012).Article

Maritzen，T.，Koo，S.J。＆Haucke，V。将平静转化为兴奋：AP180和内吞作用和疾病中的平静。生物细胞104588-602（2012）。文章

PubMed

Google Scholar

谷歌学者

Koo, S. J. et al. Vesicular Synaptobrevin/VAMP2 Levels Guarded by AP180 Control Efficient Neurotransmission. Neuron 88, 330–344 (2015).Article

Koo，S.J.等人。由AP180保护的囊泡突触素/VAMP2水平控制有效的神经传递。神经元88330-344（2015）。文章

PubMed

Google Scholar

谷歌学者

Morgan, J. R., Prasad, K., Hao, W., Augustine, G. J. & Lafer, E. M. A Conserved Clathrin Assembly Motif Essential for Synaptic Vesicle Endocytosis. J. Neurosci. 20, 8667–8676 (2000).Article

。J、神经科学。208667-8676（2000）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhuo, Y. et al. Nuclear Magnetic Resonance Structural Mapping Reveals Promiscuous Interactions between Clathrin-Box Motif Sequences and the N-Terminal Domain of the Clathrin Heavy Chain. Biochemistry 54, 2571–2580 (2015).Article

Zhuo，Y。等人。核磁共振结构图谱揭示了网格蛋白盒基序序列与网格蛋白重链N端结构域之间的混杂相互作用。生物化学542571-2580（2015）。文章

PubMed

Google Scholar

谷歌学者

Hao, W., Luo, Z., Zheng, L., Prasad, K. & Lafer, E. M. AP180 and AP-2 interact directly in a complex that cooperatively assembles clathrin. J. Biol. Chem. 274, 22785–22794 (1999).Article

Hao，W.，Luo，Z.，Zheng，L.，Prasad，K.＆Lafer，E.M。AP180和AP-2直接在协同组装网格蛋白的复合物中相互作用。化学。27422785-22794（1999）。文章

PubMed

Google Scholar

谷歌学者

Pechstein, A. et al. Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2. Proc. Natl Acad. Sci. USA 107, 4206–4211 (2010).Article

Pechstein，A。等人。通过intersectin 1和网格蛋白衔接子复合物AP2之间的复合物形成来调节突触小泡的循环。程序。国家科学院。科学。美国1074206-4211（2010）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Brett, T. J., Traub, L. M. & Fremont, D. H. Accessory protein recruitment motifs in clathrin-mediated endocytosis. Structure 10, 797–809 (2002).Article

Brett，T.J.，Traub，L.M。＆Fremont，D.H。网格蛋白介导的内吞作用中的辅助蛋白募集基序。结构10797-809（2002）。文章

PubMed

Google Scholar

谷歌学者

Erdős, G. & Dosztányi, Z. Analyzing Protein Disorder with IUPred2A. Curr. Protoc. Bioinforma. 70, e99 (2020).Article

Erds，G.和Dosztányi，Z.用IUPred2A分析蛋白质紊乱。Curr。原型。生物信息学。70，e99（2020）。文章

Google Scholar

谷歌学者

Moshkanbaryans, L., Chan, L.-S. & Graham, M. E. The Biochemical Properties and Functions of CALM and AP180 in Clathrin Mediated Endocytosis. Membranes 4, 388–413 (2014).Article

Moshkanbaryans，L.，Chan，L.-S.＆Graham，M.E。CALM和AP180在网格蛋白介导的内吞作用中的生化特性和功能。膜4388-413（2014）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Smith, S. M., Baker, M., Halebian, M. & Smith, C. J. Weak Molecular Interactions in Clathrin-Mediated Endocytosis. Front. Mol. Biosci. 4, 72 (2017).Zhang, H., Neal, S. & Wishart, D. S. RefDB: a database of uniformly referenced protein chemical shifts. J. Biomol. NMR 25, 173–195 (2003).Article .

Smith，S.M.，Baker，M.，Halebian，M。＆Smith，C.J。网格蛋白介导的内吞作用中的弱分子相互作用。正面。摩尔生物科学。。Zhang，H.，Neal，S。和Wishart，D。S。RefDB：统一参考蛋白质化学位移的数据库。J、生物摩尔。NMR 25173-195（2003）。文章。

PubMed

Google Scholar

谷歌学者

Marsh, J. A., Singh, V. K., Jia, Z. & Forman-Kay, J. D. Sensitivity of secondary structure propensities to sequence differences between α- and γ-synuclein: Implications for fibrillation. Protein Sci. 15, 2795–2804 (2006).Article

Marsh，J.A.，Singh，V.K.，Jia，Z。和Forman-Kay，J.D。二级结构倾向对α-和γ-突触核蛋白序列差异的敏感性：对纤颤的影响。蛋白质科学。152795-2804（2006）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhuo, Y. et al. Dynamic Interactions between Clathrin and Locally Structured Elements in a Disordered Protein Mediate Clathrin Lattice Assembly. J. Mol. Biol. 404, 274–290 (2010).Article

Zhuo，Y.等人。无序蛋白质中网格蛋白与局部结构元件之间的动态相互作用介导网格蛋白晶格组装。J、分子生物学。404274-290（2010）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Milles, S. et al. Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors. Cell 163, 734–745 (2015).Article

。细胞163734-745（2015）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang, L.-H., Südhof, T. C. & Anderson, R. G. W. The Appendage Domain of α-Adaptin Is a High Affinity Binding Site for Dynamin (∗). J. Biol. Chem. 270, 10079–10083 (1995).Article

Wang，L.-H.，Südhof，T.C。＆Anderson，R.G.W。α-适应性蛋白的附件结构域是动力蛋白的高亲和力结合位点（*）。J、生物。化学。27010079-10083（1995）。文章

PubMed

Google Scholar

谷歌学者

Kumar, M. et al. ELM-the Eukaryotic Linear Motif resource-2024 update. Nucleic Acids Res 52, D442–D455 (2024).Article

Kumar，M。等人。ELM真核线性基序资源-2024更新。核酸研究52，D442-D455（2024）。文章

PubMed

Google Scholar

谷歌学者

Edeling, M. A. et al. Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly. Dev. Cell 10, 329–342 (2006).Article

涉及AP-2β2附属物的分子开关调节内吞货物的选择和网格蛋白外壳的组装。Dev.Cell 10329–342（2006）。文章

PubMed

Google Scholar

谷歌学者

Zaccai, N. R. et al. FCHO controls AP2’s initiating role in endocytosis through a PtdIns(4,5)P2-dependent switch. Sci. Adv. 8, eabn2018 (2022).Article

。科学。Adv.8，eabn2018（2022）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Holehouse, A. S. & Kragelund, B. B. The molecular basis for cellular function of intrinsically disordered protein regions. Nat. Rev. Mol. Cell Biol. 1–25, https://doi.org/10.1038/s41580-023-00673-0 (2023).van der Lee, R. et al. Classification of intrinsically disordered regions and proteins.

Holehouse，A.S。＆Kragelund，B.B。内在无序蛋白质区域细胞功能的分子基础。Nat。Rev。Mol。Cell Biol。1–25，https://doi.org/10.1038/s41580-023-00673-0（2023）。van der Lee，R。等人。本质无序区域和蛋白质的分类。

Chem. Rev. 114, 6589–6631 (2014).Article .

化学。修订版1146589-6631（2014）。第[UNK]条。

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dyson, H. J. & Wright, P. E. Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6, 197–208 (2005).Article

Dyson，H.J。＆Wright，P.E。本质上非结构化的蛋白质及其功能。Nat。Rev。Mol。Cell Biol。6197-208（2005）。文章

PubMed

Google Scholar

谷歌学者

Van Roey, K. et al. Short Linear Motifs: Ubiquitous and Functionally Diverse Protein Interaction Modules Directing Cell Regulation. Chem. Rev. 114, 6733–6778 (2014).Article

Van Roey，K。等人。短线性基序：指导细胞调控的无处不在且功能多样的蛋白质相互作用模块。化学。版本1146733–6778（2014）。文章

PubMed

Google Scholar

谷歌学者

Cermakova, K. & Hodges, H. C. Interaction modules that impart specificity to disordered protein. Trends Biochemical Sci. 48, 477–490 (2023).Article

Cermakova，K。＆Hodges，H.C。相互作用模块赋予无序蛋白质特异性。趋势生化科学。48477-490（2023）。文章

Google Scholar

谷歌学者

Fung, H. Y. J., Birol, M. & Rhoades, E. IDPs in macromolecular complexes: the roles of multivalent interactions in diverse assemblies. Curr. Opin. Struct. Biol. 49, 36–43 (2018).Article

。货币。奥平。结构。生物学杂志49,36-43（2018）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sipko, E. L., Chappell, G. F. & Berlow, R. B. Multivalency emerges as a common feature of intrinsically disordered protein interactions. Curr. Opin. Struct. Biol. 84, 102742 (2024).Article

Sipko，E.L.，Chappell，G.F。＆Berlow，R.B。多价性是内在无序蛋白质相互作用的共同特征。货币。奥平。结构。生物学84102742（2024）。文章

PubMed

Google Scholar

谷歌学者

Mittag, T. et al. Dynamic equilibrium engagement of a polyvalent ligand with a single-site receptor. Proc. Natl Acad. Sci. USA 105, 17772–17777 (2008).Article

。程序。国家科学院。科学。美国10517772-17777（2008）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Elias, R. D. et al. Proline-rich domain of human ALIX contains multiple TSG101-UEV interaction sites and forms phosphorylation-mediated reversible amyloids. Proc. Natl Acad. Sci. USA 117, 24274–24284 (2020).Article

人类ALIX富含脯氨酸的结构域包含多个TSG101-UEV相互作用位点，并形成磷酸化介导的可逆淀粉样蛋白。程序。国家科学院。科学。美国11724274–24284（2020）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Day, K. J. et al. Liquid-like protein interactions catalyse assembly of endocytic vesicles. Nat. Cell Biol. 23, 366–376 (2021).Article

Day，K.J.等人。液体样蛋白质相互作用催化内吞囊泡的组装。自然细胞生物学。23366-376（2021）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kozak, M. & Kaksonen, M. Condensation of Ede1 promotes the initiation of endocytosis. Elife 11, e72865 (2022).Article

Kozak，M。＆Kaksonen，M。Ede1的缩合促进内吞作用的开始。Elife 11，e72865（2022）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yuan, F. et al. Ubiquitin-driven protein condensation promotes clathrin-mediated endocytosis. Preprint at https://doi.org/10.1101/2023.08.21.554139 (2023).Rumpf, J. et al. Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity. EMBO J.

Yuan，F。等人。泛素驱动的蛋白质缩合促进网格蛋白介导的内吞作用。预印于https://doi.org/10.1101/2023.08.21.554139（2023年）。Rumpf，J。等人。Eps15-stonin2复合物的结构为EH结构域配体特异性提供了分子解释。EMBO J。

27, 558–569 (2008).Article .

27558-569（2008）。文章。

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bugge, K. et al. Interactions by Disorder - A Matter of Context. Front. Mol. Biosci. 7, 110 (2020).Article

Bugge，K.等人，《无序的相互作用-背景问题》。正面。摩尔生物科学。7110（2020）。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Moshkanbaryans, L., Xue, J., Wark, J. R., Robinson, P. J. & Graham, M. E. A Novel Sequence in AP180 and CALM Promotes Efficient Clathrin Binding and Assembly. PLoS One 11, e0162050 (2016).Article

Moshkanbaryans，L.，Xue，J.，Wark，J.R.，Robinson，P.J。＆Graham，M.E。AP180和CALM中的一个新序列促进了有效的网格蛋白结合和组装。PLoS One 11，e0162050（2016）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Norris, F. A., Ungewickell, E. & Majerus, P. W. Inositol hexakisphosphate binds to clathrin assembly protein 3 (AP-3/AP180) and inhibits clathrin cage assembly in vitro. J. Biol. Chem. 270, 214–217 (1995).Article

Norris，F.A.，Ungewickell，E。＆Majerus，P.W。肌醇六磷酸与网格蛋白组装蛋白3（AP-3/AP180）结合并在体外抑制网格蛋白笼组装。J、生物。化学。。文章

PubMed

Google Scholar

谷歌学者

Wood, L. A., Larocque, G., Clarke, N. I., Sarkar, S. & Royle, S. J. New tools for ‘hot-wiring’ clathrin-mediated endocytosis with temporal and spatial precision. J. Cell Biol. 216, 4351–4365 (2017).Article

Wood，L.A.，Larocque，G.，Clarke，N.I.，Sarkar，S。＆Royle，S.J。具有时间和空间精度的“热接线”网格蛋白介导的内吞作用的新工具。J、细胞生物学。2164351-4365（2017）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Solyom, Z. et al. BEST-TROSY experiments for time-efficient sequential resonance assignment of large disordered proteins. J. Biomol. NMR 55, 311–321 (2013).Article

Solyom，Z.等人。大型无序蛋白质的高效时间顺序共振分配的BEST-TROSY实验。J、生物摩尔。NMR 55311-321（2013）。文章

PubMed

Google Scholar

谷歌学者

Delaglio, F. et al. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277–293 (1995).Article

Delaglio，F。等人。NMRPipe：基于UNIX管道的多维光谱处理系统。J、生物摩尔。NMR 6277-293（1995）。文章

PubMed

Google Scholar

谷歌学者

Jung, Y.-S. & Zweckstetter, M. Mars - robust automatic backbone assignment of proteins. J. Biomol. NMR 30, 11–23 (2004).Article

Jung，Y.-S.＆Zweckstetter，M。Mars-强大的蛋白质自动骨架分配。J、生物摩尔。NMR 30,11-23（2004）。文章

PubMed

Google Scholar

谷歌学者

Lee, W., Tonelli, M. & Markley, J. L. NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics 31, 1325–1327 (2015).Article

Lee，W.，Tonelli，M。＆Markley，J.L。NMRFAM-SPARKY：用于生物分子NMR光谱的增强软件。生物信息学311327-1327（2015）。文章

PubMed

Google Scholar

谷歌学者

Kazimierczuk, K. & Orekhov, V. Yu. Accelerated NMR Spectroscopy by Using Compressed Sensing. Angew. Chem. Int. Ed. 50, 5556–5559 (2011).Article

Kazimierczuk，K.&Orekhov，V.Yu。通过使用压缩传感加速NMR光谱。安吉。化学。《国际编辑》第505556-5559页（2011年）。文章

Google Scholar

谷歌学者

Skinner, S. P. et al. CcpNmr AnalysisAssign: a flexible platform for integrated NMR analysis. J. Biomol. NMR 66, 111–124 (2016).Article

Skinner，S.P.等。CcpNmr分析分配：用于集成NMR分析的灵活平台。J、生物摩尔。NMR 66111-124（2016）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lakomek, N.-A., Ying, J. & Bax, A. Measurement of 15 N relaxation rates in perdeuterated proteins by TROSY-based methods. J. Biomol. NMR 53, 209–221 (2012).Article

Lakomek，N.-A.，Ying，J.＆Bax，A.通过基于TROSY的方法测量全氘代蛋白质中的15N弛豫率。J、生物摩尔。NMR 53209-221（2012）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Guseva, S. et al. Measles virus nucleo- and phosphoproteins form liquid-like phase-separated compartments that promote nucleocapsid assembly. Sci. Adv. 6, eaaz7095 (2020).Article

麻疹病毒核蛋白和磷蛋白形成类似液体的相分离区室，促进核衣壳组装。科学。。文章

ADS

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsWe thank all members of the Milles group for fruitful discussions and critical proofreading. We thank A. Papagiannoula for recording AP2β2 assignment spectra, M.R. Jensen for providing the pET-28-GB1 plasmid, M. Blackledge and M.R. Jensen for providing analysis scripts, N.

下载参考文献致谢我们感谢Milles小组的所有成员进行了富有成果的讨论和批判性的校对。我们感谢A.Papagiannoula记录AP2β2分配光谱，M.R.Jensen提供pET-28-GB1质粒，M.Blackledge和M.R.Jensen提供分析脚本，N。

Trieloff and M. Beerbaum for technical assistance on the NMR spectrometers, and H. Nikolenko for assistance with ITC acquisition. This work used the platforms of the Grenoble Instruct-ERIC center (ISBG; UAR 3518 CNRS-CEA-UGA-EMBL) within the Grenoble Partnership for Structural Biology (PSB), supported by FRISBI (ANR-10-INBS-0005-02) and GRAL, financed within the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003), and with financial support from the TGIR-RMN-THC Fr3050 CNRS.

Trieloff和M.Beerbaum为NMR光谱仪提供技术援助，H.Nikolenko为ITC收购提供援助。这项工作使用了格勒诺布尔结构生物学伙伴关系（PSB）内的格勒诺布尔指导ERIC中心（ISBG；UAR 3518 CNRS-CEA-UGA-EMBL）的平台，由FRISBI（ANR-10-INBS-0005-02）和GRAL支持，由格勒诺布尔阿尔卑斯大学研究生院（Ecoles Universitaires de Recherche）CBH-EUR-GS（ANR-17-EURE-0003）资助，并得到TGIR-RMN-THC Fr3050 CNRS的财政支持。

We thank Caroline Mas for assistance and access to the biophysics platform. The Institut de Biologie Structurale acknowledges integration into the Interdisciplinary Research Institute of Grenoble. This work was supported by the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) (to S.M., F.L.

我们感谢Caroline Mas的帮助和访问生物物理学平台。生物结构研究所承认融入格勒诺布尔跨学科研究所。这项工作得到了莱布尼茨-福松研究所für Molekulare Pharmacologie（FMP）的支持（S.M.，f.L。

and P.S.). This project has received funding from the European Research Council (ERC) Starting Grant MultiMotif to S.M. under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 802209). We also acknowledge funding from the French National Research Agency (ANR) through an ANR T-ERC MultiMotif (ANR-17-ERC3-0004) and through the framework of the “Investissements d’Avenir” program (ANR-15-IDEX-02), DisRegulate (to S.M.).FundingOpen Access funding enabled and organized by Projekt DEAL.Author informationAuthors and AffiliationsLeibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle.

和P.S.）。该项目已获得欧洲研究理事会（ERC）的资助，根据欧盟的地平线2020研究与创新计划（第802209号赠款协议），开始向S.M.授予MultiMotif。我们还感谢法国国家研究机构（ANR）通过ANR T-ERC MultiMotif（ANR-17-ERC3-0004）和“Avenir投资”计划（ANR-15-IDEX-02）的框架提供的资金，取消了（对S.M.）的监管。资金开放获取资金由Projekt交易启用和组织。作者信息作者和附属机构Lebinz Forschungsinstitut für Molekulare Pharmacologie，Robert-rössle。

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PubMed Google ScholarContributionsS.M. conceptualized the study; M.T., K.M., S.N.F., S.M. prepared samples; S.N.F., C.A.E.R., I.M.V., P.S., S.M. performed NMR experiments and analysis; P.L.J., F.L. performed MS experiments and analysis; M.T., C.A.E.R. and I.M.V. performed ITC experiments; S.M.

PubMed谷歌学术贡献。M、将研究概念化；M、 T.，K.M.，S.N.F.，S.M.制备的样品；S、 N.F.，C.A.E.R.，I.M.V.，P.S.，S.M.进行了NMR实验和分析；P、 L.J.，F.L.进行了MS实验和分析；M、 T.，C.A.E.R.和I.M.V.进行了ITC实验；S、 M。

and S.N.F. wrote the manuscript with help from all authors.Corresponding authorCorrespondence to.

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Reprints and permissionsAbout this articleCite this articleNaudi-Fabra, S., Elena-Real, C.A., Vedel, I.M. et al. An extended interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis.

转载和许可本文引用本文Naudi Fabra，S.，Elena Real，C.A.，Vedel，I.M.等人。扩展的相互作用位点决定了网格蛋白介导的内吞作用中AP180和AP2之间的结合。

Nat Commun 15, 5884 (2024). https://doi.org/10.1038/s41467-024-50212-4Download citationReceived: 27 February 2024Accepted: 03 July 2024Published: 13 July 2024DOI: https://doi.org/10.1038/s41467-024-50212-4Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

《国家公社》155884（2024）。https://doi.org/10.1038/s41467-024-50212-4Download引文收到日期：2024年2月27日接受日期：2024年7月3日发布日期：2024年7月13日OI：https://doi.org/10.1038/s41467-024-50212-4Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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