RRC ID 73460
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)