Structural basis for the recognition of kinesin family member 21A (KIF21A) by the ankyrin domains of KANK1 and KANK2 proteins
Structural basis for the recognition of kinesin family member 21A (KIF21A) by the ankyrin domains of KANK1 and KANK2 proteins
复制标题
KANK1 和 KANK2 蛋白的锚蛋白结构域识别驱动蛋白家族成员 21A (KIF21A) 的结构基础。
DOI：
10.1074/jbc.m117.817494
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发表时间：
2018-01-12
影响因子：
4.8
通讯作者：
Xu, Chao
中科院分区：
文献类型：
--
作者：
Guo, Qiong;Liao, Shanhui;Xu, Chao
良好控制的微管组织对于细胞内运输、细胞骨架维持和细胞发育是必不可少的。KANK家族成员KN基序和锚蛋白重复结构域蛋白1（KANK1）通过其C端锚蛋白结构域将驱动蛋白家族成员21 A（KIF21 A）募集到细胞皮层来控制微管的生长。然而，KANK1锚蛋白结构域如何识别KIF21A以及其他KANK蛋白是否也可以结合KIF21A仍然未知。在这里，使用结构，定点诱变和生物化学研究的组合，我们发现KIF21A中约22个氨基酸的延伸足以结合KANK1及其同源物KANK2。我们进一步解决了KIF21A肽与KANK1锚蛋白结构域或KANK2锚蛋白结构域的复杂结构。在每个复合物中，KIF21A被锚蛋白结构域的两个不同的口袋识别，并在结合锚蛋白结构域时采用螺旋构象。阐明KANK结构可能会促进我们的理解KANK1作为一个支架分子在控制微管生长在细胞周边的作用。
A well-controlled microtubule organization is essential for intracellular transport, cytoskeleton maintenance, and cell development. KN motif and ankyrin repeat domain-containing protein 1 (KANK1), a member of KANK family, recruits kinesin family member 21A (KIF21A) to the cell cortex to control microtubule growth via its C-terminal ankyrin domain. However, how the KANK1 ankyrin domain recognizes KIF21A and whether other KANK proteins can also bind KIF21A remain unknown. Here, using a combination of structural, site-directed mutagenesis, and biochemical studies, we found that a stretch of approximate to 22 amino acids in KIF21A is sufficient for binding to KANK1 and its close homolog KANK2. We further solved the complex structure of the KIF21A peptide with either the KANK1 ankyrin domain or the KANK2 ankyrin domain. In each complex, KIF21A is recognized by two distinct pockets of the ankyrin domain and adopts helical conformations upon binding to the ankyrin domain. The elucidated KANK structures may advance our understanding of the role of KANK1 as a scaffolding molecule in controlling microtubule growth at the cell periphery.