Kinesin-microtubule interaction reveals the mechanism of kinesin-1 for discriminating the binding site on microtubule

【摘要】 Microtubule catalyzes the mechanochemical cycle of kinesin, a kind of molecular motor, through its crucial roles in kinesin’s gating, ATPase and force-generation process. These functions of microtubule are realized through the kinesin-microtubule interaction. The binding site of kinesin on the microtubule surface is fixed. For most of the kinesin-family members, the binding site on microtubule is in the groove between α-tubulin and β-tubulin in a protofilament. The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear. Using the molecular dynamics simulation method, we investigate the interactions between kinesin-1 and the different binding positions on microtubule.The key non-bonded interactions between the motor domain and tubulins in kinesin’s different nucleotide-binding states are listed. The differences of the amino-acid sequences between α-and β-tubulins make kinesin-1 binding to the α–β groove much more favorable than to the β–α groove. From these results, a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed. Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule, the mechanism may also be shared by other family members of kinesin.更多还原

【Abstract】 Microtubule catalyzes the mechanochemical cycle of kinesin, a kind of molecular motor, through its crucial roles in kinesin’s gating, ATPase and force-generation process. These functions of microtubule are realized through the kinesin-microtubule interaction. The binding site of kinesin on the microtubule surface is fixed. For most of the kinesin-family members, the binding site on microtubule is in the groove between α-tubulin and β-tubulin in a protofilament. The mechanism of kinesin searching for the appropriate binding site on microtubule is still unclear. Using the molecular dynamics simulation method, we investigate the interactions between kinesin-1 and the different binding positions on microtubule.The key non-bonded interactions between the motor domain and tubulins in kinesin’s different nucleotide-binding states are listed. The differences of the amino-acid sequences between α-and β-tubulins make kinesin-1 binding to the α–β groove much more favorable than to the β–α groove. From these results, a two-step mechanism of kinesin-1 to discriminate the correct binding site on microtubule is proposed. Most of the kinesin-family members have the conserved motor domain and bind to the same site on microtubule, the mechanism may also be shared by other family members of kinesin.更多还原