Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14

• DOI: 10.1101/2020.06.01.128371
• Publication Date: 2020-06-03T02:05:12Z
• Authors: Matthieu P.M.H. B...; Ana B. Asenjo; Mohammadjavad Paydar; Sabin Dhakal; Benjamin H. Kwok; Hernando Sosa
• Keywords: Kinesin; Linker; Conformational change

Abstract KIF14 is a mitotic kinesin protein important for cytokinesis. Its overexpression associated with variety of cancers and mutations in result cerebral renal development defects. Like other kinesins, contains highly conserved catalytic motor domain where the energy from ATP hydrolysis converted to directed movement along microtubules. Although much known regarding molecular mechanism motility, there lack structural information kinesin-microtubule interactions at sufficient resolution unambiguously assess how conformational changes related hydrolysis, microtubule binding translocation are coupled. Here we determined near-atomic cryo-electron microscopy structures five different constructs bound microtubules presence nucleotide analogues mimicking distinct steps ATPase cycle. Eighteen independent together supporting functional assays provide comprehensive view occurring binding. Our data shows that: 1) induces opening pocket; 2) AMP-PNP ADP-AlF x induce closure pocket this change allosterically controlled by neck-linker domain; 3) when undocked prevents nucleotide-binding-pocket fully close dampens hydrolysis; 4) fifteen residues required assume docked conformation; 5) analogue adopts configuration an open nucleotide-binding-pocket; 6) position controls step rather than cycle; 7) two domains dimer adopt conformations simultaneously microtubule. These observations basis coordinated chemo-mechanical plus end model.