Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion

Pan, Wenfei1; Sun, Kang1,2; Tang, Kun1,3; Xiao, Qingpin1,4; Ma, Chenxue1; Yu, Cong1,2; Wei, Zhiyi1

2018-02-09

10.1074/jbc.M117.815779

JOURNAL OF BIOLOGICAL CHEMISTRY   影响因子和分区

0021-9258

1083-351X

Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of scaffold proteins, playing critical roles in cytoskeleton organization, cell polarity, and migration. Mutations in KANK proteins are implicated in cancers and genetic diseases, such as nephrotic syndrome. KANK proteins can bind various target proteins through different protein regions, including a highly conserved ankyrin repeat domain (ANKRD). However, the molecular basis for target recognition by the ANKRD remains elusive. In this study, we solved a high-resolution crystal structure of the ANKRD of KANK1 in complex with a short sequence of the motor protein kinesin family member 21A (KIF21A), revealing that the highly specific target-binding mode of the ANKRD involves combinatorial use of two interfaces. Mutations in either interface disrupted the KANK1-KIF21A interaction. Cellular immunofluorescence localization analysis indicated that binding-deficient mutations block recruitment of KIF21A to focal adhesions by KANK1. In conclusion, our structural study provides mechanistic explanations for the ANKRD-mediated recognition of KIF21A and for many disease-related mutations identified in human KANK proteins.

crystal structure focal adhesion protein complex scaffold protein tumor suppressor gene KANK ankyrin repeat

SCI ; EI

英语

第一 ; 通讯

Shenzhen Science and Technology Innovation Commission[JCYJ20160229153100269] ; Shenzhen Science and Technology Innovation Commission[ZDSYS20140509142721429]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000424948000010

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

20180704806563

Adhesion ; Binding energy ; Crystal structure ; Proteins

Biomedical Engineering:461.1 ; Physical Chemistry:801.4 ; Organic Compounds:804.1 ; Crystal Lattice:933.1.1 ; Materials Science:951

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Dept Biol, Shenzhen 518055, Peoples R China
2.Shenzhen Key Lab Cell Microenvironm, Guangdong Prov Key Lab Cell Microenvironm & Dis R, Shenzhen 518055, Peoples R China
3.Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China
4.Univ Macau, Fac Hlth Sci, Taipa, Macau, Peoples R China

Pan, Wenfei,Sun, Kang,Tang, Kun,et al. Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(6):1944-1956.

Pan, Wenfei.,Sun, Kang.,Tang, Kun.,Xiao, Qingpin.,Ma, Chenxue.,...&Wei, Zhiyi.(2018).Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion.JOURNAL OF BIOLOGICAL CHEMISTRY,293(6),1944-1956.

Pan, Wenfei,et al."Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion".JOURNAL OF BIOLOGICAL CHEMISTRY 293.6(2018):1944-1956.