Reference - Detail
|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.|
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.
|MeSH||Humans Microtubule-Associated Proteins* / metabolism Microtubules / metabolism Nucleotides / metabolism Polymers / metabolism Tubulin* / metabolism|
|DNA material||CSII-CMV-MCS (RDB04377)|