The helically extended SH3 domain of the T cell adaptor protein ADAP is a novel lipid interaction domain
The helically extended SH3 domain of the T cell adaptor protein ADAP is a novel lipid interaction domain
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DOI：
10.1016/j.jmb.2005.02.069
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发表时间：
2005-05-13
影响因子：
5.6
通讯作者：
Freund, C
中科院分区：
文献类型：
--
作者：
Heuer, K;Arbuzova, A;Freund, C
粘附和脱颗粒促进衔接蛋白（ADAP）是关键参与下游信号事件触发的T细胞受体的激活。T细胞的细胞因子产生、增殖和整合素聚集依赖于ADAP功能，但这些过程的分子基础知之甚少。我们现在显示ADAP的hSH 3结构域是一个脂质相互作用模块，与酸性脂质（包括磷脂酰肌醇）结合。带正电的表面。该结构域优先结合。与多价酸性脂质如PIP 2或PIP 3的相互作用依赖于hSH 3结构域折叠的N-末端螺旋。来自SH 3支架的碱性氨基酸侧链也有助于脂质结合。在T细胞信号传导的背景下，我们的研究结果表明，ADAP，在招聘到细胞-细胞连接作为一个多蛋白复合物的一部分，直接与质膜的磷酸肌醇富集区相互作用。此外，ADAP脂质相互作用将螺旋延伸的SH 3支架定义为膜相互作用结构域的新成员。(c)2005爱思唯尔有限公司保留所有权利。
Adhesion and degranulation-promoting adapter protein (ADAP) is critically involved in downstream signalling events triggered by the activation of the T cell receptor. Cytokine production, proliferation and integrin clustering of T cells are dependent on ADAP function, but the molecular basis for these processes is poorly understood. We now show the hSH3 domain of ADAP to be a lipid-interaction module that binds to acidic lipids, including phosphatidylinositides. Positively charged surface patches of. the domain preferentially bind. to polyvalent acidic lipids such as PIP2 or PIP3 over the monovalent PS phospholipid and this interaction is dependent on the N-terminal helix of the hSH3 domain fold. Basic amino acid side-chains from the SH3 scaffold also contribute to lipid binding. In the context of T cell signalling, our findings suggest that ADAP, upon recruitment to the cell-cell junction as part of a multiprotein complex, directly interacts with phosphoinositide-enriched regions of the plasma membrane. Furthermore, the ADAP lipid interaction defines the helically extended SH3 scaffold as a novel member of membrane interaction domains. (c) 2005 Elsevier Ltd. All rights reserved.