The structure of the N-terminus of kindlin-1: a domain important for alphaiibbeta3 integrin activation.
The structure of the N-terminus of kindlin-1: a domain important for alphaiibbeta3 integrin activation.
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DOI：
10.1016/j.jmb.2009.09.061
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发表时间：
2009-12-18
影响因子：
5.6
通讯作者：
Critchley DR
中科院分区：
文献类型：
--
作者：
Goult BT;Bouaouina M;Harburger DS;Bate N;Patel B;Anthis NJ;Campbell ID;Calderwood DA;Barsukov IL;Roberts GC;Critchley DR
异源二聚体细胞粘附分子的整联蛋白家族以低亲和力和高亲和力状态存在，并且整联蛋白活化需要talin FERM（四点一、埃兹蛋白、根蛋白、膜突蛋白）结构域与β-整联蛋白胞质结构域中的膜近端序列结合。然而，它最近变得明显，Kindlin家族的FERM结构域蛋白质也是必不可少的塔林诱导的整合素激活。FERM结构域通常由F1、F2和F3结构域组成，但talin FERM结构域是非典型的，因为它在F1中包含一个大的插入片段，并且前面是一个以前未识别的结构域F0。初步的序列比对显示，kindlin FERM结构域与talin FERM结构域最相似，但同源性似乎仅限于F2和F3结构域。基于对塔林FERM结构域的详细表征，我们重新研究了与kindlin的序列关系，现在表明kindlin确实包含与塔林FERM结构域相同的结构域结构。然而，kindlin F1结构域包含比talin F1更大的插入片段，这破坏了序列比对。插入片段的长度在不同的kindlin中不同，它并不保守，而且和talin一样，很大程度上是非结构化的。我们已经确定了kindlin-1的F0结构域的NMR，这表明它采用了相同的泛素样折叠的talin F0和F1结构域。kindlin-1和talin F0结构域的比较确定了与kindlin-1 F1结构域的可能界面。Kindlin F0与其他蛋白质相互作用的潜在位点进行了讨论，包括Kindlin-1，Kindlin-2和Kindlin-3之间不同的位点。我们还证明，F0是kindlin-1支持talin诱导的αIIbβ3整合素活化的能力以及kindlin-1定位于粘着斑所必需的。
The integrin family of heterodimeric cell adhesion molecules exists in both low- and high-affinity states, and integrin activation requires binding of the talin FERM (four-point-one, ezrin, radixin, moesin) domain to membrane-proximal sequences in the β-integrin cytoplasmic domain. However, it has recently become apparent that the kindlin family of FERM domain proteins is also essential for talin-induced integrin activation. FERM domains are typically composed of F1, F2, and F3 domains, but the talin FERM domain is atypical in that it contains a large insert in F1 and is preceded by a previously unrecognized domain, F0. Initial sequence alignments showed that the kindlin FERM domain was most similar to the talin FERM domain, but the homology appeared to be restricted to the F2 and F3 domains. Based on a detailed characterization of the talin FERM domain, we have reinvestigated the sequence relationship with kindlins and now show that kindlins do indeed contain the same domain structure as the talin FERM domain. However, the kindlin F1 domain contains an even larger insert than that in talin F1 that disrupts the sequence alignment. The insert, which varies in length between different kindlins, is not conserved and, as in talin, is largely unstructured. We have determined the structure of the kindlin-1 F0 domain by NMR, which shows that it adopts the same ubiquitin-like fold as the talin F0 and F1 domains. Comparison of the kindlin-1 and talin F0 domains identifies the probable interface with the kindlin-1 F1 domain. Potential sites of interaction of kindlin F0 with other proteins are discussed, including sites that differ between kindlin-1, kindlin-2, and kindlin-3. We also demonstrate that F0 is required for the ability of kindlin-1 to support talin-induced αIIbβ3 integrin activation and for the localization of kindlin-1 to focal adhesions.
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影响因子：
5.8
作者：
Glaser, F;Pupko, T;Ben-Tal, N
通讯作者：
Ben-Tal, N
DOI：
10.1111/j.1742-4658.2009.06893.x
发表时间：
2009-03
期刊：
The FEBS journal
影响因子：
--
作者：
Debrand E;El Jai Y;Spence L;Bate N;Praekelt U;Pritchard CA;Monkley SJ;Critchley DR
通讯作者：
Critchley DR
影响因子：
4.8
作者：
Calderwood, DA;Tai, V;Ginsberg, MH
通讯作者：
Ginsberg, MH
影响因子：
7.5
作者：
Boettcher, Ralph T.;Lange, Anika;Faessler, Reinhard
通讯作者：
Faessler, Reinhard
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.