2W0P

Crystal structure of the filamin A repeat 21 complexed with the migfilin peptide

2W0P の概要

• エントリーDOI: 10.2210/pdb2w0p/pdb
• 関連するPDBエントリー: 2AAV 2BP3 2BRQ 2J3S 2JF1
• 分子名称: FILAMIN-A, FILAMIN-BINDING LIM PROTEIN 1, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: alternative splicing, cytoskeleton-complex, phosphoprotein, disease mutation, immunoglobulin like, zinc, filamin, complex, integrin, migfilin, receptor, polymorphism, cytoskeleton, actin-binding, cell junction, cell adhesion, metal-binding, cytoplasm, lim domain, cell shape, acetylation
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm, cell cortex: P21333 Q8WUP2
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 21220.36

構造登録者

Ruskamo, S.,Ylanne, J. (登録日: 2008-08-20, 公開日: 2008-09-30, 最終更新日: 2023-12-13)

主引用文献

Lad, Y.,Jiang, P.,Ruskamo, S.,Harburger, D.S.,Ylanne, J.,Campbell, I.D.,Calderwood, D.A.
Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin {Beta} Tails.
J.Biol.Chem., 283:35154-, 2008

PubMed Abstract: A link between sites of cell adhesion and the cytoskeleton is essential for regulation of cell shape, motility, and signaling. Migfilin is a recently identified adaptor protein that localizes at cell-cell and cell-extracellular matrix adhesion sites, where it is thought to provide a link to the cytoskeleton by interacting with the actin cross-linking protein filamin. Here we have used x-ray crystallography, NMR spectroscopy, and protein-protein interaction studies to investigate the molecular basis of migfilin binding to filamin. We report that the N-terminal portion of migfilin can bind all three human filamins (FLNa, -b, or -c) and that there are multiple migfilin-binding sites in FLNa. Human filamins are composed of an N-terminal actin-binding domain followed by 24 immunoglobulin-like (IgFLN) domains and we find that migfilin binds preferentially to IgFLNa21 and more weakly to IgFLNa19 and -22. The filamin-binding site in migfilin is localized between Pro(5) and Pro(19) and binds to the CD face of the IgFLNa21 beta-sandwich. This interaction is similar to the previously characterized beta 7 integrin-IgFLNa21 interaction and migfilin and integrin beta tails can compete with one another for binding to IgFLNa21. This suggests that competition between filamin ligands for common binding sites on IgFLN domains may provide a general means of modulating filamin interactions and signaling. In this specific case, displacement of integrin tails from filamin by migfilin may provide a mechanism for switching between different integrin-cytoskeleton linkages.

PubMed: 18829455
DOI: 10.1074/JBC.M802592200

実験手法

X-RAY DIFFRACTION (1.9 Å)