调控KIF1A二聚化和活性的潜在的磷酸化位点(英文)  

Potential Phosphorylation Site Modulates The Dimerization and Activity of KIF1A

作　　者：刘贝[1,2] 岳旸[2] 俞勇[2] 任锦启 冯巍[2] 霍麟[2] 徐涛[1,2] 

机构地区：[1]华中科技大学生命科学与技术学院,武汉430074 [2]中国科学院生物物理研究所,生物大分子国家重点实验室,北京100101

出　　处：《生物化学与生物物理进展》2014年第9期870-876,821,共7页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Basic Research Program of China(2010CB833701,2011CB910503,2014CB910202);The National Natural Science Foundation of China(31130065,31300611,31190062,31200577)~~

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.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.

关 键 词：KIF1A 磷酸化 二聚化 轴突运输 

分 类 号：Q71[生物学—分子生物学]