Structural studies on full-length talin1 reveal a compact auto-inhibited dimer: implications for talin activation.

Structural studies on full-length talin1 reveal a compact auto-inhibited dimer: implications for talin activation.
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DOI:
10.1016/j.jsb.2013.05.014
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发表时间:
2013-10
影响因子:
3
通讯作者:
Hanein, Dorit
Hanein, Dorit
中科院分区:
生物学3区
文献类型:
--
作者:
Goult, Benjamin T.;Xu, Xiao-Ping;Gingras, Alexandre R.;Swift, Mark;Patel, Bipin;Bate, Neil;Kopp, Petra M.;Barsukov, Igor L.;Critchley, David R.;Volkmann, Niels;Hanein, Dorit

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Talin是一种大的衔接蛋白,其激活整合素并将其偶联到细胞骨架肌动蛋白。Talin含有连接到柔性杆的N-末端FERM(带4.1、埃兹蛋白、根蛋白、膜突蛋白)结构域(头部),所述柔性杆由13个两亲性螺旋束(R1-R13)组成,所述两亲性螺旋束终止于形成反平行二聚体的C-末端螺旋(DD)。我们推导出一个三维结构模型的全长塔林在分辨率约为2.5 nm,使用EM重建全长塔林和已知的形状的各个域和域间的角度,来自小角度X射线散射。塔林采用与二聚体一致的紧凑构象,其中两个塔林棒形成甜甜圈状结构,两个塔林头并排包装占据这个甜甜圈中心的孔。在这种结构中,整合素结合位点的头部域和肌动蛋白结合位点的羧基末端的杆被掩盖,这意味着塔林必须解开之前,它可以支持整合素激活和从事肌动蛋白细胞骨架。
Talin is a large adaptor protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM (band 4.1, ezrin, radixin, moesin) domain (the head) linked to a flexible rod comprised of 13 amphipathic helical bundles (R1–R13) that terminate in a C-terminal helix (DD) that forms an anti-parallel dimer. We derived a three-dimensional structural model of full-length talin at a resolution of approximately 2.5 nm using EM reconstruction of full-length talin and the known shapes of the individual domains and inter-domain angles as derived from small angle X-ray scattering. Talin adopts a compact conformation consistent with a dimer in which the two talin rods form a donut-shaped structure, with the two talin heads packed side by side occupying the hole at the center of this donut. In this configuration, the integrin binding site in the head domain and the actin-binding site at the carboxy-terminus of the rod are masked, implying that talin must unravel before it can support integrin activation and engage the actin cytoskeleton.
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