論文 - 詳細
RRC ID | 73460 |
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著者 | Luo W, Demidov V, Shen Q, Girão H, Chakraborty M, Maiorov A, Ataullakhanov FI, Lin C, Maiato H, Grishchuk EL. |
タイトル | CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner. |
ジャーナル | Sci Adv |
Abstract |
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. |
巻・号 | 9(1) |
ページ | eabq5404 |
公開日 | 2023-1-4 |
DOI | 10.1126/sciadv.abq5404 |
PMID | 36598991 |
PMC | PMC9812398 |
MeSH | Humans Microtubule-Associated Proteins* / metabolism Microtubules / metabolism Nucleotides / metabolism Polymers / metabolism Tubulin* / metabolism |
IF | 13.117 |
リソース情報 | |
遺伝子材料 | CSII-CMV-MCS (RDB04377) |