2W0P

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

Summary for 2W0P

• Entry DOI: 10.2210/pdb2w0p/pdb
• Related: 2AAV 2BP3 2BRQ 2J3S 2JF1
• Descriptor: FILAMIN-A, FILAMIN-BINDING LIM PROTEIN 1, SULFATE ION, ... (4 entities in total)
• Functional Keywords: 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
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cell cortex: P21333 Q8WUP2
• Total number of polymer chains: 3
• Total formula weight: 21220.36

Authors

Ruskamo, S.,Ylanne, J. (deposition date: 2008-08-20, release date: 2008-09-30, Last modification date: 2023-12-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)