Structural determinants and functional consequences of protein affinity for membrane rafts.
Structural determinants and functional consequences of protein affinity for membrane rafts.
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DOI：
10.1038/s41467-017-01328-3
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发表时间：
2017-10-31
影响因子：
16.6
通讯作者：
Levental I
中科院分区：
文献类型：
--
作者：
Lorent JH;Diaz-Rohrer B;Lin X;Spring K;Gorfe AA;Levental KR;Levental I
真核细胞质膜被划分为功能性的横向结构域，包括脂质驱动的膜筏。筏通过选择性募集和保留特定蛋白质参与大多数质膜功能。然而，跨膜蛋白分配到筏结构域的结构决定因素尚未完全了解。假设蛋白质跨膜结构域（TMDs）决定筏协会，在这里，我们直接量化筏亲和力几十个TMDs。我们确定了三个物理特征，独立影响筏分区，即TMD表面积，长度和棕榈酰化。我们将这些发现合理化为一个机械的物理模型，该模型预测来自蛋白质序列的筏亲和力。将这些概念应用于人类蛋白质组揭示质膜蛋白具有比细胞内膜更高的筏亲和力，这与筏介导的质膜分选一致。总的来说，我们的实验观察和物理模型建立一般规则筏分区的TMDs和支持膜交通中的中心作用的筏。脂筏是质膜结构域，特异性地募集特定的蛋白质。在这里，作者表明，表面积，长度和棕榈酰化的单程跨膜结构域是至关重要的筏分区，并提出了一个通用的模型来预测蛋白质与筏协会。
Eukaryotic plasma membranes are compartmentalized into functional lateral domains, including lipid-driven membrane rafts. Rafts are involved in most plasma membrane functions by selective recruitment and retention of specific proteins. However, the structural determinants of transmembrane protein partitioning to raft domains are not fully understood. Hypothesizing that protein transmembrane domains (TMDs) determine raft association, here we directly quantify raft affinity for dozens of TMDs. We identify three physical features that independently affect raft partitioning, namely TMD surface area, length, and palmitoylation. We rationalize these findings into a mechanistic, physical model that predicts raft affinity from the protein sequence. Application of these concepts to the human proteome reveals that plasma membrane proteins have higher raft affinity than those of intracellular membranes, consistent with raft-mediated plasma membrane sorting. Overall, our experimental observations and physical model establish general rules for raft partitioning of TMDs and support the central role of rafts in membrane traffic. Lipid rafts are plasma membrane domains that specifically recruit particular proteins. Here, the authors show that the surface area, length and palmitoylation of single-pass transmembrane domains are crucial for raft partitioning and propose a general model to predict protein association with rafts.
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影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
DOI：
10.1083/jcb.200901145
发表时间：
2009-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Klemm RW;Ejsing CS;Surma MA;Kaiser HJ;Gerl MJ;Sampaio JL;de Robillard Q;Ferguson C;Proszynski TJ;Shevchenko A;Simons K
通讯作者：
Simons K
影响因子：
4.8
作者：
Garcia-Saez, Ana J.;Chiantia, Salvatore;Schwille, Petra
通讯作者：
Schwille, Petra
DOI：
10.1073/pnas.1200773109
发表时间：
2012-05-22
影响因子：
11.1
作者：
Janosi, Lorant;Li, Zhenlong;Gorfe, Alemayehu A.
通讯作者：
Gorfe, Alemayehu A.
影响因子：
4.1
作者：
Levental, Ilya;Byfield, Fitzroy J.;Janmey, Paul A.
通讯作者：
Janmey, Paul A.