4K92

A Cryptic TOG Domain with a Distinct Architecture Underlies CLASP-Dependent Bipolar Spindle Formation

Summary for 4K92

• Entry DOI: 10.2210/pdb4k92/pdb
• Descriptor: CLIP-associating protein 1 (2 entities in total)
• Functional Keywords: heat-repeat tog domain, regulator of microtubule dynamics, tubulin, cytoplasm microtubule cytoskeleton, structural protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton: Q7Z460
• Total number of polymer chains: 2
• Total formula weight: 61771.36

Authors

Leano, J.B.,Rogers, S.L.,Slep, K.C. (deposition date: 2013-04-19, release date: 2013-06-12, Last modification date: 2024-10-30)

Primary citation

Leano, J.B.,Rogers, S.L.,Slep, K.C.
A cryptic TOG domain with a distinct architecture underlies CLASP-dependent bipolar spindle formation.
Structure, 21:939-950, 2013

PubMed Abstract: CLASP 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.

PubMed: 23727231
DOI: 10.1016/j.str.2013.04.018

Experimental method

X-RAY DIFFRACTION (2.005 Å)