5YAY

Crystal structure of KANK1/KIF21A complex

5YAY の概要

• エントリーDOI: 10.2210/pdb5yay/pdb
• 分子名称: KN motif and ankyrin repeat domains 1, Kinesin-like protein KIF21A (3 entities in total)
• 機能のキーワード: scaffold protein, ank repeat, protein binding
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton : Q9QXL2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31007.50

構造登録者

Wei, Z.,Pan, W. (登録日: 2017-09-02, 公開日: 2017-12-20, 最終更新日: 2023-11-22)

主引用文献

Pan, W.,Sun, K.,Tang, K.,Xiao, Q.,Ma, C.,Yu, C.,Wei, Z.
Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion.
J. Biol. Chem., 293:1944-1956, 2018

PubMed Abstract: 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.

PubMed: 29217769
DOI: 10.1074/jbc.M117.815779

実験手法

X-RAY DIFFRACTION (1.55 Å)