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

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.