2brq
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The ability of adhesion receptors to transmit biochemical signals and | + | The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the high-resolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin beta cytoplasmic tail forms an extended beta strand that interacts with beta strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notably, the structurally defined filamin binding site overlaps with that of the integrin-regulator talin, and these proteins compete for binding to integrin tails, allowing integrin-filamin interactions to impact talin-dependent integrin activation. Phosphothreonine-mimicking mutations inhibit filamin, but not talin, binding, indicating that kinases may modulate this competition and provide additional means to control integrin functions. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Kiema, T | + | [[Category: Kiema, T R.]] |
[[Category: Ylanne, J.]] | [[Category: Ylanne, J.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: receptor]] | [[Category: receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:40:56 2008'' |
Revision as of 14:40, 21 February 2008
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CRYSTAL STRUCTURE OF THE FILAMIN A REPEAT 21 COMPLEXED WITH THE INTEGRIN BETA7 CYTOPLASMIC TAIL PEPTIDE
Contents |
Overview
The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the high-resolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin beta cytoplasmic tail forms an extended beta strand that interacts with beta strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notably, the structurally defined filamin binding site overlaps with that of the integrin-regulator talin, and these proteins compete for binding to integrin tails, allowing integrin-filamin interactions to impact talin-dependent integrin activation. Phosphothreonine-mimicking mutations inhibit filamin, but not talin, binding, indicating that kinases may modulate this competition and provide additional means to control integrin functions.
Disease
Known diseases associated with this structure: Frontometaphyseal dysplasia OMIM:[300017], Heterotopia, periventricular OMIM:[300017], Heterotopia, periventricular nodular, with frontometaphyseal dysplasia OMIM:[300017], Heterotopia, periventricular, ED variant OMIM:[300017], Melnick-Needles syndrome OMIM:[300017], Otopalatodigital syndrome, type I OMIM:[300017], Otopalatodigital syndrome, type II OMIM:[300017]
About this Structure
2BRQ is a Protein complex structure of sequences from Homo sapiens with and as ligands. Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.
Reference
The molecular basis of filamin binding to integrins and competition with talin., Kiema T, Lad Y, Jiang P, Oxley CL, Baldassarre M, Wegener KL, Campbell ID, Ylanne J, Calderwood DA, Mol Cell. 2006 Feb 3;21(3):337-47. PMID:16455489
Page seeded by OCA on Thu Feb 21 16:40:56 2008
