2j3s

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PDB ID 2j3s

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, resolution 2.50Å
Sites: , , , , and
Ligands: , ,
Related: 2BP3, 2JF1, 2AAV, 2BRQ


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



CRYSTAL STRUCTURE OF THE HUMAN FILAMIN A IG DOMAINS 19 TO 21


Overview

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.

About this Structure

2J3S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of three tandem filamin domains reveals auto-inhibition of ligand binding., Lad Y, Kiema T, Jiang P, Pentikainen OT, Coles CH, Campbell ID, Calderwood DA, Ylanne J, EMBO J. 2007 Sep 5;26(17):3993-4004. Epub 2007 Aug 9. PMID:17690686

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