CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner.
CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner.
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DOI：
10.1126/sciadv.abq5404
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发表时间：
2023-01-04
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
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CLASP（细胞质接头相关蛋白）是微管动力学的普遍稳定剂，但其在微管加端的分子靶点尚不清楚。使用DNA折纸为基础的重建，我们表明，人类CLASP 2簇形成一个承重债券与终端非GTP微管蛋白在稳定的微管尖端。这种活性依赖于CLASP 2的非常规TOG 2结构域，其在非GTP二聚体转化为聚合能力的GTP-微管蛋白时释放其与非GTP二聚体的高亲和力键。CLASP 2识别核苷酸特异性微管蛋白构象并稳定促进灾难的非GTP微管蛋白的能力与先前未被充分认识的末端微管蛋白处GDP和GTP之间的交换交织在一起。我们建议，TOG 2依赖的稳定偶发发生的非GTP微管蛋白代表了一个独特的分子机制，以抑制灾难的自由组装微管末端，并促进持久的微管蛋白组装在承重拴系的末端，如在分裂细胞的动粒。基于DNA折纸的CLASP 2簇的微管结合揭示了一种独特的正末端稳定机制。
CLASPs (cytoplasmic linker-associated proteins) are ubiquitous stabilizers of microtubule dynamics, but their molecular targets at the microtubule plus-end are not understood. Using DNA origami–based reconstructions, we show that clusters of human CLASP2 form a load-bearing bond with terminal non-GTP tubulins at the stabilized microtubule tip. This activity relies on the unconventional TOG2 domain of CLASP2, which releases its high-affinity bond with non-GTP dimers upon their conversion into polymerization-competent GTP-tubulins. The ability of CLASP2 to recognize nucleotide-specific tubulin conformation and stabilize the catastrophe-promoting non-GTP tubulins intertwines with the previously underappreciated exchange between GDP and GTP at terminal tubulins. We propose that TOG2-dependent stabilization of sporadically occurring non-GTP tubulins represents a distinct molecular mechanism to suppress catastrophe at the freely assembling microtubule ends and to promote persistent tubulin assembly at the load-bearing tethered ends, such as at the kinetochores in dividing cells. Microtubule-binding by DNA origami-based clusters of CLASP2 reveals a distinct mechanism of plus-end stabilization.
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影响因子：
64.5
作者：
Akhmanova, A;Hoogenraad, CC;Galjart, N
通讯作者：
Galjart, N
影响因子：
11.8
作者：
Al-Bassam, Jawdat;Kim, Hwajin;Brouhard, Gary;van Oijen, Antoine;Harrison, Stephen C.;Chang, Fred
通讯作者：
Chang, Fred
影响因子：
16.6
作者：
Chakraborty, Manas;Tarasovetc, Ekaterina, V;Grishchuk, Ekaterina L.
通讯作者：
Grishchuk, Ekaterina L.
DOI：
10.1038/s43586-020-00009-8
发表时间：
2021-01-28
期刊：
NATURE REVIEWS METHODS PRIMERS
影响因子：
--
作者：
Dey, Swarup;Fan, Chunhai;Zhan, Pengfei
通讯作者：
Zhan, Pengfei
影响因子：
11.8
作者：
Aher A;Kok M;Sharma A;Rai A;Olieric N;Rodriguez-Garcia R;Katrukha EA;Weinert T;Olieric V;Kapitein LC;Steinmetz MO;Dogterom M;Akhmanova A
通讯作者：
Akhmanova A