A Small Peptide Sequence is Sufficient for Initiating Kinesin-1 Activation Through Part of TPR Region of KLC1
A Small Peptide Sequence is Sufficient for Initiating Kinesin-1 Activation Through Part of TPR Region of KLC1
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DOI：
10.1111/j.1600-0854.2012.01350.x
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发表时间：
2012-06-01
期刊：
影响因子：
4.5
通讯作者：
Suzuki, Toshiharu
中科院分区：
文献类型：
--
作者：
Kawano, Takanori;Araseki, Masahiko;Suzuki, Toshiharu
当蛋白质相互作用将其从抑制状态激活时，驱动蛋白-1顺行运输含有货物蛋白的囊泡。驱动蛋白-1货物蛋白Alcadeina（Alca）的C-末端胞质区域与KLC 1亚基的四肽重复（TPR）区域相互作用，激活驱动蛋白-1与囊泡和顺行运输的关联。我们发现Alca细胞质区域的两个10-氨基酸WD基序中的任何一个都是启动这种激活所必需的。人工跨膜蛋白含有WD基序诱导驱动蛋白-1的囊泡协会和顺行运输的KLC依赖性的方式，即使在正常抑制过量KLC 1的存在下，从而使我们能够分析KLC 1 TPR-WD功能的相互作用，在体内详细。WD基序的TPR区域的一部分被激活驱动蛋白-1和转运，表明在体内只有部分TPR结构是激活驱动蛋白-1和转运所必需的。对于不同的驱动蛋白-1货物蛋白，JIP 1，一个11个氨基酸的C-末端区域足以招募KLC 1囊泡，但没有激活运输。这些观察结果表明，结构不同的TPR相互作用肽可能有不同的影响驱动蛋白-1。这种机制可以部分解释驱动蛋白1如何组织各种货物分子的运输。
Kinesin-1 anterogradely transports vesicles containing cargo proteins when a proteinprotein interaction activates it from an inhibited state. The C-terminal cytoplasmic region of kinesin-1 cargo protein Alcadeina (Alca) interacts with the KLC1 subunit's tetratricopeptide repeat (TPR) region, activating kinesin-1's association with vesicles and anterograde transport. We found that either of two 10-amino-acid WD motifs in Alca cytoplasmic region was necessary and sufficient to initiate this activation. An artificial transmembrane protein containing either WD motif induced kinesin-1's vesicular association and anterograde transport in a KLC-dependent manner, even in the normally inhibiting presence of excess KLC1, thus allowing us to analyze the KLC1 TPR-WD functional interaction in detail in vivo. A part of TPR region was dispensable for the WD motifs' activation of kinesin-1 and transport, indicating that only part of the TPR structure is required for this function in vivo. For a different kinesin-1 cargo protein, JIP1, an 11-amino-acid C-terminal region was sufficient to recruit KLC1 to vesicles, but did not activate transport. These observations suggest that structurally different TPR-interacting peptides may have different effects on kinesin-1. This mechanism may partly explain how kinesin-1 can organize the transport of a wide variety of cargo molecules.