| RRC ID |
73460
|
| Author |
Luo W, Demidov V, Shen Q, Girão H, Chakraborty M, Maiorov A, Ataullakhanov FI, Lin C, Maiato H, Grishchuk EL.
|
| Title |
CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner.
|
| Journal |
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.
|
| Volume |
9(1)
|
| Pages |
eabq5404
|
| Published |
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
|
| Resource |
| DNA material |
CSII-CMV-MCS (RDB04377) |
