The structural basis of the talin-KANK1 interaction that coordinates the actin and microtubule cytoskeletons at focal adhesions.
The structural basis of the talin-KANK1 interaction that coordinates the actin and microtubule cytoskeletons at focal adhesions.
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作者：
细胞和细胞外基质之间的粘附是由异二聚体 (αβ) 整联蛋白受体介导的，这些受体在细胞内与收缩肌动球蛋白机制相连。控制这种联系的蛋白质之一是talin，它将胞质信号蛋白组织成β-整合素尾部的离散复合物，称为粘着斑（FA）。接头蛋白 KANK1 与 FA 区域（称为粘附带）的踝蛋白结合。在这里，我们采用非共价晶体伴侣来解析 talin-KANK1 复合物。该结构揭示了 KANK1 的踝蛋白结合 KN 区域包含一个新的基序，其中 β-发夹稳定了 α-螺旋区域，这解释了其与踝蛋白 R7 的特异性相互作用和高亲和力。从结构中鉴定出的 KANK1 中的单点突变体消除了相互作用，使我们能够检查粘附带中 KANK1 的富集情况。引人注目的是，在表达组成型活性形式的纽蛋白的细胞中，即使在存在肌球蛋白抑制剂的情况下也能保持 FA 结构完整，即使在肌动球蛋白张力释放时，KANK1 也定位于整个 FA 结构。我们提出了一个模型，通过肌动球蛋白对踝蛋白的作用力消除了 FA 中心的踝蛋白结合中的 KANK1，同时将其保留在粘附外围。
Adhesion between cells and the extracellular matrix is mediated by heterodimeric (αβ) integrin receptors that are intracellularly linked to the contractile actomyosin machinery. One of the proteins that control this link is talin, which organizes cytosolic signalling proteins into discrete complexes on β-integrin tails referred to as focal adhesions (FAs). The adapter protein KANK1 binds to talin in the region of FAs known as the adhesion belt. Here, we adapted a non-covalent crystallographic chaperone to resolve the talin–KANK1 complex. This structure revealed that the talin binding KN region of KANK1 contains a novel motif where a β-hairpin stabilizes the α-helical region, explaining both its specific interaction with talin R7 and high affinity. Single point mutants in KANK1 identified from the structure abolished the interaction and enabled us to examine KANK1 enrichment in the adhesion belt. Strikingly, in cells expressing a constitutively active form of vinculin that keeps the FA structure intact even in the presence of myosin inhibitors, KANK1 localizes throughout the entire FA structure even when actomyosin tension is released. We propose a model whereby actomyosin forces on talin eliminate KANK1 from talin binding in the centre of FAs while retaining it at the adhesion periphery.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
15
作者：
Maita, Nobuo
通讯作者：
Maita, Nobuo
DOI：
10.1016/j.jbc.2021.100837
发表时间：
2021-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Gough RE;Jones MC;Zacharchenko T;Le S;Yu M;Jacquemet G;Muench SP;Yan J;Humphries JD;Jørgensen C;Humphries MJ;Goult BT
通讯作者：
Goult BT
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
塔林的C末端肌动蛋白结合结构域的结构。
影响因子：
11.4
作者：
Gingras, Alexandre R.;Bate, Neil;Goult, Benjamin T.;Hazelwood, Larnele;Canestrelli, Ilona;Grossmann, J. Gunter;Liu, HongJun;Putz, Nicholas S. M.;Roberts, Gordon C. K.;Volkmann, Niels;Hanein, Dorit;Barsukov, Igor L.;Critchley, David R.
通讯作者：
Critchley, David R.