CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner.

Wangxi Luo, Vladimir Demidov, Qi Shen, Hugo Girão, Manas Chakraborty, Aleksandr Maiorov, Fazly I Ataullakhanov, Chenxiang Lin, Helder Maiato, Ekaterina L Grishchuk

Science advances 2023 Jan 04

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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.

Citation

Wangxi Luo, Vladimir Demidov, Qi Shen, Hugo Girão, Manas Chakraborty, Aleksandr Maiorov, Fazly I Ataullakhanov, Chenxiang Lin, Helder Maiato, Ekaterina L Grishchuk. CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state-sensitive manner. Science advances. 2023 Jan 04;9(1):eabq5404