title: Nucleotide-dependent structural fluctuations and regulation of microtubule-binding affinity of KIF1A.
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 α4 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 α4. These results suggest that KIF1A regulates affinity to MT by changing the flexibility of the helix α4 during the ATP hydrolysis process: the binding site becomes more flexible in the strong binding state than in the weak binding state.
authors: Cybermedia Center, Osaka University, Toyonaka, 560-0043, Japan; Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, 606-8502, Japan.
authors: Ryo
authors: R
authors: Kanada
authors: Fumiko
authors: F
authors: Takagi
authors: Macoto
authors: M
authors: Kikuchi
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D016547:Kinesins / Q000737:chemistry*; D051379:Mice; D008870:Microtubules / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: C490576:Kif1a protein, mouse; D000255:Adenosine Triphosphate; D016547:Kinesins
keywords: Gō-like model; allosteric enzyme; kinesin; molecular dynamics; molecular motor