中文摘要：

驱动蛋白kinesin-3家族中的KIF1A蛋白主要参与轴突上分泌囊泡前体的正向运输.KIF1A中的CC1-FHA片段能够形成稳定的二聚体结构,同时促进驱动蛋白的活性,但是其具体的调节机制尚未清楚.基于已有的CC1-FHA二聚体的晶体结构,我们发现在二聚体表面的＂487SPKK490＂位置存在潜在的磷酸化位点.证明了将487位点模拟磷酸化后将导致CC1-FHA二聚体的解聚.进一步,在487位点进行点突变将影响KIF1A的活性以及线虫中KIF1A介导的突触囊泡在轴突上的运输.因此,高度保守的＂487SPKK490＂可能对CC1-FHA片段二聚化和调节KIF1A活性起着关键性作用.

英文摘要：

Kinesin-3 KIFIA is responsible for the anterograde transport of synapse vesicle （SV） precursors in axons. The CC1-FHA tandem of KIFIA has been revealed as a stable dimer that can trigger motor activity, but the mechanism underlying the regulation of the CC 1-FHA dimer is unclear. Based on the CC 1-FHA dimer structure, we found a potential phosphorylation motif ＂487SPKK490＂ located at the dimer interface. We demonstrated that the phosphorylation-mimetic mutation of Ser487 leads to the dissociation of the CC1-FHA dimer. Moreover, the Ser487-mutation could regulate the motor activity of KIF1A and the KIF1A-mediated axonal transport activity of SVs in C. elegans. Thus, the highly conserved ＂487SPKK490＂ motif may be a key site in the CC1-FHA tandem for regulating CC1-FHA dimerization and the subsequent activity of KIF1 A.