6VGU

Crystal structure of FERM-folded talin head domain bound to the NPLY motif of beta3-integrin

6VGU の概要

• エントリーDOI: 10.2210/pdb6vgu/pdb
• 関連するPDBエントリー: 3ivf
• 分子名称: Integrin beta-3,Talin-1 (2 entities in total)
• 機能のキーワード: talin, ferm-fold, nply motif, integrin, signaling protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50382.75

構造登録者

Zhang, P.,Sun, Y.,Wu, J. (登録日: 2020-01-09, 公開日: 2020-12-16, 最終更新日: 2023-10-11)

主引用文献

Zhang, P.,Azizi, L.,Kukkurainen, S.,Gao, T.,Baikoghli, M.,Jacquier, M.C.,Sun, Y.,Maatta, J.A.E.,Cheng, R.H.,Wehrle-Haller, B.,Hytonen, V.P.,Wu, J.
Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding.
Proc.Natl.Acad.Sci.USA, 117:32402-32412, 2020

PubMed Abstract: Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been crystallized in an unexpected, elongated form. This form, however, lacks a C-terminal fragment and possesses reduced β3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the β3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of β3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the β3-integrin cytoplasmic segment. Removal of the poly-lysine motif or disrupting the FERM-folded configuration of the talin head significantly impairs integrin activation and clustering. Therefore, structural characterization of the FERM-folded active talin head provides fundamental understanding of the regulatory mechanism of integrin function.

PubMed: 33288722
DOI: 10.1073/pnas.2014583117

実験手法

X-RAY DIFFRACTION (2.78 Å)