An unconventional TOG domain is required for CLASP localization.
An unconventional TOG domain is required for CLASP localization.
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DOI：
10.1016/j.cub.2023.07.009
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发表时间：
2023-08-21
期刊：
影响因子：
9.2
通讯作者：
Dumont, Julien
中科院分区：
文献类型：
--
作者：
Gareil, Nelly;Gervais, Alison;Macaisne, Nicolas;Chevreux, Guillaume;Canman, Julie C.;Andreani, Jessica;Dumont, Julien
细胞质接头相关蛋白（CLASP）是微管相关蛋白（MAP）的一个保守家族，通过促进拯救同时抑制灾难来维持微管的生长状态。CLASP功能涉及肿瘤过表达基因（TOG）结构域的有序阵列，并通过保守的C-末端结构域（CTD）与多个蛋白质伴侣结合。在迁移细胞中，CLASP通过其CTD与粘着斑蛋白PHLDB 2/LL 5 β结合，作为皮质微管稳定复合物（CMSC）的一部分集中在粘着斑附近的皮质。皮质CLASP还稳定微管的子集，其刺激粘着斑周转并产生朝向迁移细胞的前缘的极化微管网络。CLASP也通过其CTD和高尔基体蛋白GCC 185之间的相互作用被募集到反式高尔基体网络（TGN）。这使得微管向迁移细胞的前沿生长，这是高尔基体组织，极化细胞内运输和细胞运动所必需的。在分裂细胞中，CLASP在着丝粒上对于有效的染色体分离和后期纺锤体完整性是必不可少的。CENP-E和ASTRIN都将CLASP结合并靶向于着丝粒，尽管这种相互作用所需的CLASP结构域尚不清楚。尽管它的高度进化保守，CTD仍然结构不明。在这里，我们发现，CTD可以在结构上建模为一个TOG域。我们确定了CLASP CTD与伴侣蛋白相互作用所必需的表面暴露和保守的精氨酸残基。总之，我们的研究结果提供了CLASP CTD在整个细胞周期中指导不同亚细胞定位的结构机制。CLASP CTD折叠为非常规TOG结构域一种进化上保守的精氨酸介导与多个CLASP伴侣的相互作用新的人类CLASP 1直接和间接相互作用物的鉴定Golgin蛋白GOLGA 4是CLASP正确的高尔基定位所必需的Gareil和热尔韦等人.证明CLASPs的C-末端结构域（CTD）折叠为非常规TOG结构域，其已被重新利用以作为调控模块发挥功能。CTD介导适当的CLASP亚细胞定位通过结合到多个合作伙伴通过进化保守的精氨酸。
Cytoplasmic linker-associated proteins (CLASPs) form a conserved family of microtubule-associated proteins (MAPs) that maintain microtubules in a growing state by promoting rescue while suppressing catastrophe. CLASP function involves an ordered array of tumor overexpressed gene (TOG) domains and binding to multiple protein partners via a conserved C-terminal domain (CTD). In migrating cells, CLASPs concentrate at the cortex near focal adhesions as part of cortical microtubule stabilization complexes (CMSCs), via binding of their CTD to the focal adhesion protein PHLDB2/LL5β. Cortical CLASPs also stabilize a subset of microtubules, which stimulate focal adhesion turnover and generate a polarized microtubule network toward the leading edge of migrating cells. CLASPs are also recruited to the trans-Golgi network (TGN) via an interaction between their CTD and the Golgin protein GCC185. This allows microtubule growth toward the leading edge of migrating cells, which is required for Golgi organization, polarized intracellular transport, and cell motility. In dividing cells, CLASPs are essential at kinetochores for efficient chromosome segregation and anaphase spindle integrity. Both CENP-E and ASTRIN bind and target CLASPs to kinetochores, although the CLASP domain required for this interaction is not known. Despite its high evolutionary conservation, the CTD remains structurally uncharacterized. Here, we find that the CTD can be structurally modeled as a TOG domain. We identify a surface-exposed and conserved arginine residue essential for CLASP CTD interaction with partner proteins. Together, our results provide a structural mechanism by which the CLASP CTD directs diverse sub-cellular localizations throughout the cell cycle. The CLASP CTD folds as an unconventional TOG domain An evolutionarily conserved arginine mediates interaction with multiple CLASP partners Identification of novel human CLASP1 direct and indirect interactors The Golgin protein GOLGA4 is required for proper Golgi localization of CLASP Gareil and Gervais et al. demonstrate that the C-terminal domain (CTD) of CLASPs folds as an unconventional TOG domain, which has been repurposed to function as a regulatory module. The CTD mediates proper CLASP sub-cellular localization by binding to multiple partners through an evolutionarily conserved arginine.
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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
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影响因子：
11.8
作者：
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通讯作者：
Chang, Fred
影响因子：
7.7
作者：
Macaisne N;Bellutti L;Laband K;Edwards F;Pitayu-Nugroho L;Gervais A;Ganeswaran T;Geoffroy H;Maton G;Canman JC;Lacroix B;Dumont J
通讯作者：
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影响因子：
64.5
作者：
Akhmanova, A;Hoogenraad, CC;Galjart, N
通讯作者：
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影响因子：
11.8
作者：
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通讯作者：
Akhmanova A