Premium
Nucleotide‐dependent structural fluctuations and regulation of microtubule‐binding affinity of KIF1A
Author(s) -
Kanada Ryo,
Takagi Fumiko,
Kikuchi Macoto
Publication year - 2015
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24780
Subject(s) - kinesin , helix (gastropod) , biophysics , molecular dynamics , nucleotide , atp hydrolysis , microtubule , thermal fluctuations , molecular motor , binding site , chemistry , plasma protein binding , biology , microbiology and biotechnology , biochemistry , physics , enzyme , computational chemistry , gene , atpase , thermodynamics , ecology , snail
Molecular motors such as kinesin regulate affinity to a rail protein during the ATP hydrolysis cycle. The regulation mechanism, however, is yet to be determined. To understand this mechanism, we investigated the structural fluctuations of the motor head of the single‐headed kinesin called KIF1A in different nucleotide states using molecular dynamics simulations of a Gō‐like model. We found that the helix α 4 at the microtubule (MT) binding site intermittently exhibits a large structural fluctuation when MT is absent. Frequency of this fluctuation changes systematically according to the nucleotide states and correlates strongly with the experimentally observed binding affinity to MT. We also showed that thermal fluctuation enhances the correlation and the interaction with the nucleotide suppresses the fluctuation of the helix α 4 . These results suggest that KIF1A regulates affinity to MT by changing the flexibility of the helix α 4 during the ATP hydrolysis process: the binding site becomes more flexible in the strong binding state than in the weak binding state. Proteins 2015; 83:809–819. © 2015 Wiley Periodicals, Inc.