| 调控KIF1A二聚化和活性的潜在的磷酸化位点 |
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| 引用本文： | 刘贝,岳旸,俞勇,任锦启,冯巍,霍琳,徐涛.调控KIF1A二聚化和活性的潜在的磷酸化位点[J].生物化学与生物物理进展,2014,41(9):870-876. |
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| 作者姓名： | 刘贝 岳旸 俞勇 任锦启 冯巍 霍琳 徐涛 |
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| 作者单位： | 华中科技大学生命科学与技术学院,武汉 430074;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,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,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,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,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,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,华中科技大学生命科学与技术学院,武汉 430074;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 |
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| 基金项目： | 国家重点基础研究发展计划(2010CB833701, 2011CB910503, 2014CB910202)和国家自然科学基金(31130065, 31300611, 31190062, 31200577)资助项目 |
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| 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.
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| 关 键 词： | KIFA 磷酸化 二聚化 轴突运输 |
| 收稿时间： | 2014/3/17 0:00:00 |
| 修稿时间： | 2014/5/30 0:00:00 |
Potential Phosphorylation Site Modulates The Dimerization and Activity of KIF1A |
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| LIU Bei,YUE Yang,YU Yong,REN Jin-Qi,FENG Wei,HUO Lin and XU Tao.Potential Phosphorylation Site Modulates The Dimerization and Activity of KIF1A[J].Progress In Biochemistry and Biophysics,2014,41(9):870-876. |
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| Authors: | LIU Bei YUE Yang YU Yong REN Jin-Qi FENG Wei HUO Lin and XU Tao |
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| Institution: | College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China and College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China |
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| Abstract: | Kinesin-3 KIF1A is responsible for the anterograde transport of synapse vesicle (SV) precursors in axons. The CC1-FHA tandem of KIF1A has been revealed as a stable dimer that can trigger motor activity, but the mechanism underlying the regulation of the CC1-FHA dimer is unclear. Based on the CC1-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 KIF1A. |
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| Keywords: | KIF1A phosphorylation dimerization axonal transport |
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