4k92
From Proteopedia
A Cryptic TOG Domain with a Distinct Architecture Underlies CLASP-Dependent Bipolar Spindle Formation
Structural highlights
FunctionCLAP1_HUMAN Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedCLASP is a key regulator of microtubule (MT) dynamics and bipolar mitotic spindle structure with CLASP mutants displaying a distinctive monopolar spindle phenotype. It has been postulated that cryptic TOG domains underlie CLASP's ability to regulate MT dynamics. Here, we report the crystal structure of a cryptic TOG domain (TOG2) from human CLASP1, demonstrating the presence of a TOG array in the CLASP family. Strikingly, CLASP1 TOG2 exhibits a convex architecture across the tubulin-binding surface that contrasts with the flat tubulin-binding surface of XMAP215 family TOG domains. Mutations in key conserved TOG2 determinants abrogate the ability of CLASP mutants to rescue bipolar spindle formation in Drosophila cells depleted of endogenous CLASP. These findings highlight the common mechanistic use of TOG domains in XMAP215 and CLASP families to regulate MT dynamics and suggest that differential TOG domain architecture may confer distinct functions to these critical cytoskeletal regulators. A Cryptic TOG Domain with a Distinct Architecture Underlies CLASP-Dependent Bipolar Spindle Formation.,Leano JB, Rogers SL, Slep KC Structure. 2013 May 29. pii: S0969-2126(13)00130-5. doi:, 10.1016/j.str.2013.04.018. PMID:23727231[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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