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KIF14[391-755] dimer two-heads-bound state - ADP-AlFx in complex with a microtubule
Structural highlights
FunctionKIF14_MOUSE Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (PubMed:24949858). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (By similarity). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (By similarity). Regulates cell growth through regulation of cell cycle progression and cytokinesis. During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (By similarity). During late neurogenesis, regulates the cerebellar and cerebral cortex development and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (PubMed:23308235, PubMed:24931760). Also is required for chromosome congression and alignment during mitotic cell cycle process (By similarity). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (By similarity).[UniProtKB:Q15058][1] [2] [3] Publication Abstract from PubMedKIF14 is a mitotic kinesin whose malfunction is associated with cerebral and renal developmental defects and several cancers. Like other kinesins, KIF14 couples ATP hydrolysis and microtubule binding to the generation of mechanical work, but the coupling mechanism between these processes is still not fully clear. Here we report 20 high-resolution (2.7-3.9 A) cryo-electron microscopy KIF14-microtubule structures with complementary functional assays. Analysis procedures were implemented to separate coexisting conformations of microtubule-bound monomeric and dimeric KIF14 constructs. The data provide a comprehensive view of the microtubule and nucleotide induced KIF14 conformational changes. It shows that: 1) microtubule binding, the nucleotide species, and the neck-linker domain govern the transition between three major conformations of the motor domain; 2) an undocked neck-linker prevents the nucleotide-binding pocket to fully close and dampens ATP hydrolysis; 3) 13 neck-linker residues are required to assume a stable docked conformation; 4) the neck-linker position controls the hydrolysis rather than the nucleotide binding step; 5) the two motor domains of KIF14 dimers adopt distinct conformations when bound to the microtubule; and 6) the formation of the two-heads-bound-state introduces structural changes in both motor domains of KIF14 dimers. These observations provide the structural basis for a coordinated chemo-mechanical kinesin translocation model. Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14.,Benoit MPMH, Asenjo AB, Paydar M, Dhakal S, Kwok BH, Sosa H Nat Commun. 2021 Jun 15;12(1):3637. doi: 10.1038/s41467-021-23581-3. PMID:34131133[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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