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Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion
Pan, Wenfei; Sun, Kang; Tang, Kun; Xiao, Qingpin; Ma, Chenxue; Yu, Cong; Wei, Zhiyi
2018-02-09
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume293Issue:6Pages:1944-1956
AbstractKidney 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.
Keywordcrystal structure focal adhesion protein complex scaffold protein tumor suppressor gene KANK ankyrin repeat
DOI10.1074/jbc.M117.815779
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000424948000010
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
The Source to ArticleWOS
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
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GB/T 7714
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.
APA 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.
MLA 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.
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