Nucleotide‐dependent structural fluctuations and regulation of microtubule‐binding affinity of KIF1A |
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Authors: | Ryo Kanada Fumiko Takagi Macoto Kikuchi |
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Affiliation: | 1. Cybermedia Center, Osaka University, Toyonaka, Japan;2. Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan;3. Department of Applied Physics, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan;4. Department of Physics, Osaka University, Toyonaka, Japan;5. Graduate School of Frontier Bioscience, Osaka University, Suita, Japan |
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Abstract: | 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 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 . These results suggest that KIF1A regulates affinity to MT by changing the flexibility of the helix 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. |
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Keywords: | molecular motor kinesin allosteric enzyme molecular dynamics Gō ‐like model |
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