Role of the Helix in Talin F3 Domain (F3 Helix) in Talin-Mediated Integrin Activation
Role of the Helix in Talin F3 Domain (F3 Helix) in
Talin-Mediated Integrin Activation
复制标题
Talin F3 结构域螺旋（F3 螺旋）在 Talin 介导的整合素激活中的作用
DOI：
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发表时间：
2017
影响因子：
2.6
通讯作者：
Weiming Hu
中科院分区：
文献类型：
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作者：
Ang Li;Q. Guo;Ai;Yaliang Zhou;Weiming Hu
配体与细胞整合素结合（活化）的增加在血小板和白细胞功能中起重要作用。Talin在体内是整合素αIIbβ3活化所必需的，在体外是充分的。talin激活整合素的确切机制仍在阐明中。特别是，塔林经历构象变化（围绕F3螺旋），并插入F3螺旋到脂质双层;然而，这种脂质插入机制的塔林和塔林的能力，激活整合素之间的连接从未被探索过。在这项工作中，我们使用合理的诱变，建模细胞系统，和结构建模研究膜诱导的塔林构象变化的潜在作用，塔林介导的整合素激活。talin F3螺旋插入膜的关键残基的突变完全废除了talin介导的整合素活化，而不影响talin与整合素的结合。此外，talin F3螺旋中的脂质结合序列的突变显著降低了talin激活整合素的能力。我们的研究结果表明，F3螺旋可能有助于塔林介导的整合素激活。
Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin’s capacity to activate integrin has never been explored before. In this work, we used rational mutagenesis, modeled cell systems, and structural modeling to study the potential role of membrane-induced talin conformational changes in talin-mediated integrin activation. Mutations of the residues critical for talin F3 helix to insert into membrane completely abolished talin-mediated integrin activation without affecting the binding of talin to integrins. Furthermore, mutations of the lipid-binding sequences in talin F3 helix significantly reduced the capacity of talin to activate integrin. Our results suggest that the F3 helix may contribute to talin-mediated integrin activation.
影响因子：
16
作者：
Zhu, Jieqing;Luo, Bing-Hao;Barth, Patrick;Schonbrun, Jack;Baker, David;Springer, Timothy A.
通讯作者：
Springer, Timothy A.