6WWG

KIF14[391-772] dimer two-heads-bound state - ADP-AlFx in complex with a microtubule

Summary for 6WWG

• Entry DOI: 10.2210/pdb6wwg/pdb
• EMDB information: 21932 21933 21934 21935 21936 21937 21938 21939 21940 21941 21942 21943 21944 21945 21946 21947 21948 21949
• Descriptor: Kinesin-like protein KIF14, Tubulin alpha-1B chain, Tubulin beta-2B chain, ... (9 entities in total)
• Functional Keywords: kif14, kinesin, motility, microtubule, tubulin, motor protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 292084.59

Authors

Benoit, M.P.M.H.,Asenjo, A.B.,Paydar, M.,Dhakal, S.,Kwok, B.,Sosa, H. (deposition date: 2020-05-09, release date: 2021-05-05, Last modification date: 2024-05-29)

Primary citation

Benoit, M.P.M.H.,Asenjo, A.B.,Paydar, M.,Dhakal, S.,Kwok, B.H.,Sosa, H.
Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14.
Nat Commun, 12:3637-3637, 2021

PubMed Abstract: KIF14 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 Å) 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.

PubMed: 34131133
DOI: 10.1038/s41467-021-23581-3

Experimental method

ELECTRON MICROSCOPY (2.9 Å)