4y05

KIF2C short Loop2 constructKIF2C short Loop2 construct

Structural highlights 4y05 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.59Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KIF2C_HUMAN In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis. Publication Abstract from PubMed Kinesin-13 proteins depolymerize microtubules in an ATP hydrolysis dependent manner. The coupling between these two activities remains unclear. Here, we first studied the role of the kinesin-13 subfamily specific Loop2 and of the KVD motif at the tip of this loop. Shortening the loop, the Lysine/Glutamate interchange and the additional Val-to-Ser substitution all led to Kif2C mutants with decreased microtubule-stimulated ATPase and impaired depolymerization capability. We rationalized these results based on a structural model of the Kif2C-ATP-tubulin complex derived from the recently determined structures of kinesin-1 bound to tubulin. In this model, upon microtubule binding Kif2C undergoes a conformational change governed in part by the interaction of the KVD motif with the tubulin interdimer interface. Second, we mutated to an Alanine the conserved Glutamate residue of the Switch2 nucleotide binding motif. This mutation blocks motile kinesins in a post-conformational change state and inhibits ATP hydrolysis. This Kif2C mutant still depolymerized microtubules and yielded complexes of one Kif2C with two tubulin heterodimers. These results demonstrate that the structural change of Kif2C-ATP upon binding to microtubule ends is sufficient for tubulin release whereas ATP hydrolysis is not required. Overall our data suggest that the conformation reached by kinesin-13s upon tubulin binding is similar to that of tubulin-bound, ATP-bound, motile kinesins but that this conformation is adapted to microtubule depolymerization. New insights into the coupling between microtubule depolymerization and ATP hydrolysis by kinesin-13 protein Kif2C.,Wang W, Shen T, Guerois R, Zhang F, Kuerban H, Lv Y, Gigant B, Knossow M, Wang C J Biol Chem. 2015 Jun 8. pii: jbc.M115.646919. PMID:26055718 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4y05, resolution 2.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image