2J3S

Crystal structure of the human filamin A Ig domains 19 to 21

2J3S の概要

• エントリーDOI: 10.2210/pdb2j3s/pdb
• 関連するPDBエントリー: 2AAV 2BP3 2BRQ 2JF1
• 分子名称: FILAMIN-A, BROMIDE ION, 1,4-DIETHYLENE DIOXIDE, ... (5 entities in total)
• 機能のキーワード: cytoskeleton, phosphorylation, structural protein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm, cell cortex: P21333
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61796.27

構造登録者

Kiema, T.-R.,Ylanne, J. (登録日: 2006-08-23, 公開日: 2007-10-16, 最終更新日: 2023-12-13)

主引用文献

Lad, Y.,Kiema, T.-R.,Jiang, P.,Pentikanen, O.T.,Coles, C.H.,Campbell, I.D.,Calderwood, D.A.,Ylanne, J.
Structure of Three Tandem Filamin Domains Reveals Auto-Inhibition of Ligand-Binding.
Embo J., 26:3993-, 2007

PubMed Abstract: Human filamins are large actin-crosslinking proteins composed of an N-terminal actin-binding domain followed by 24 Ig-like domains (IgFLNs), which interact with numerous transmembrane receptors and cytosolic signaling proteins. Here we report the 2.5 A resolution structure of a three-domain fragment of human filamin A (IgFLNa19-21). The structure reveals an unexpected domain arrangement, with IgFLNa20 partially unfolded bringing IgFLNa21 into close proximity to IgFLNa19. Notably the N-terminus of IgFLNa20 forms a beta-strand that associates with the CD face of IgFLNa21 and occupies the binding site for integrin adhesion receptors. Disruption of this IgFLNa20-IgFLNa21 interaction enhances filamin binding to integrin beta-tails. Structural and functional analysis of other IgFLN domains suggests that auto-inhibition by adjacent IgFLN domains may be a general mechanism controlling filamin-ligand interactions. This can explain the increased integrin binding of filamin splice variants and provides a mechanism by which ligand binding might impact filamin structure.

PubMed: 17690686
DOI: 10.1038/SJ.EMBOJ.7601827

実験手法

X-RAY DIFFRACTION (2.5 Å)