Structural analyses of key features in the KANK1 center dot KIF21A complex yield mechanistic insights into the cross-talk between microtubules and the cell cortex

doi:10.1074/jbc.M117.816017

	Structural analyses of key features in the KANK1 center dot KIF21A complex yield mechanistic insights into the cross-talk between microtubules and the cell cortex
	Weng, Zhuangfeng1,2 ; Shang, Yuan 3,5; Yao, Deqiang 1; Zhu, Jinwei 1; Zhang, Rongguang1,2,4
	2018-01-05
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY (IF:4.0[JCR-2023],4.4[5-Year])
ISSN	0021-9258
卷号	293 期号:1 页码:215-225
发表状态	已发表
DOI	10.1074/jbc.M117.816017
摘要	The cross-talk between dynamic microtubules and the cell cortex plays important roles in cell division, polarity, and migration. A critical adaptor that links the plus ends of microtubules with the cell cortex is the KANK N-terminal motif and ankyrin repeat domains 1 (KANK1)/kinesin family member 21A (KIF21A) complex. Genetic defects in these two proteins are associated with various cancers and developmental diseases, such as congenital fibrosis of the extraocular muscles type 1. However, the molecular mechanism governing the KANK1/KIF21A interaction and the role of the conserved ankyrin (ANK) repeats in this interaction are still unclear. In this study, we present the crystal structure of the KANK1 center dot KIF21A complex at 2.1 angstrom resolution. The structure, together with biochemical studies, revealed that a five-helix-bundle-capping domain immediately preceding the ANK repeats of KANK1 forms a structural and functional supramodule with its ANK repeats in binding to an evolutionarily conserved peptide located in the middle of KIF21A. We also show that several missense mutations present in cancer patients are located at the interface of the KANK1 center dot KIF21A complex and destabilize its formation. In conclusion, our study elucidates the molecular basis underlying the KANK1/KIF21A interaction and also provides possible mechanistic explanations for the diseases caused by mutations in KANK1 and KIF21A.
收录类别	SCI ; SCIE ; EI
语种	英语
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDB08030104]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000419453200019
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20180204632680
EI主题词	Cell proliferation ; Cells ; Crystal structure ; Cytology ; Diseases
EI分类号	Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Crystal Lattice:933.1.1
WOS关键词	MUSCLES TYPE-1 CFEOM1 ; SPINDLE ORIENTATION ; CONGENITAL FIBROSIS ; ADHESION DYNAMICS ; KINESIN KIF21A ; KANK PROTEINS ; MIGRATION ; ENDS ; MUTATIONS ; ACTIN
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/16245
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_张荣光组生命科学与技术学院_博士生
通讯作者	Zhu, Jinwei; Zhang, Rongguang
作者单位	1.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab M, Natl Ctr Prot Sci Shanghai,Univ Chinese Acad Sci, 333 Haike Rd, Shanghai 201203, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 3.Hong Kong Univ Sci & Technol, Div Life Sci, State Key Lab Mol Neurosci, Kowloon, Hong Kong, Peoples R China 4.Chinese Acad Sci, Shanghai Res Ctr, Shanghai 200031, Peoples R China 5.Univ Arizona, Ctr Biomed Informat & Biostat, Tucson, AZ 85721 USA
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Weng, Zhuangfeng,Shang, Yuan,Yao, Deqiang,et al. Structural analyses of key features in the KANK1 center dot KIF21A complex yield mechanistic insights into the cross-talk between microtubules and the cell cortex[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(1):215-225.
APA	Weng, Zhuangfeng,Shang, Yuan,Yao, Deqiang,Zhu, Jinwei,&Zhang, Rongguang.(2018).Structural analyses of key features in the KANK1 center dot KIF21A complex yield mechanistic insights into the cross-talk between microtubules and the cell cortex.JOURNAL OF BIOLOGICAL CHEMISTRY,293(1),215-225.
MLA	Weng, Zhuangfeng,et al."Structural analyses of key features in the KANK1 center dot KIF21A complex yield mechanistic insights into the cross-talk between microtubules and the cell cortex".JOURNAL OF BIOLOGICAL CHEMISTRY 293.1(2018):215-225.