2brq
From Proteopedia
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|PDB= 2brq |SIZE=350|CAPTION= <scene name='initialview01'>2brq</scene>, resolution 2.10Å | |PDB= 2brq |SIZE=350|CAPTION= <scene name='initialview01'>2brq</scene>, resolution 2.10Å | ||
|SITE= <scene name='pdbsite=AC1:Gtt+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Gtt+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+A'>AC3</scene> and <scene name='pdbsite=AC4:Gol+Binding+Site+For+Chain+A'>AC4</scene> | |SITE= <scene name='pdbsite=AC1:Gtt+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Gtt+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+A'>AC3</scene> and <scene name='pdbsite=AC4:Gol+Binding+Site+For+Chain+A'>AC4</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSW:D-GAMMA-GLUTAMYL-L-CYSTEINYLGLYCINE'>GSW</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2bp3|2BP3]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2brq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brq OCA], [http://www.ebi.ac.uk/pdbsum/2brq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2brq RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Frontometaphyseal dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Heterotopia, periventricular OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Heterotopia, periventricular nodular, with frontometaphyseal dysplasia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Heterotopia, periventricular, ED variant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Melnick-Needles syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Otopalatodigital syndrome, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]], Otopalatodigital syndrome, type II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300017 300017]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Kiema, T R.]] | [[Category: Kiema, T R.]] | ||
[[Category: Ylanne, J.]] | [[Category: Ylanne, J.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: GSW]] | ||
[[Category: actin-binding]] | [[Category: actin-binding]] | ||
[[Category: cell adhesion]] | [[Category: cell adhesion]] | ||
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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 Mon Mar 31 02:10:46 2008'' |
Revision as of 23:10, 30 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Ligands: | , | ||||||
| Related: | 2BP3
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE FILAMIN A REPEAT 21 COMPLEXED WITH THE INTEGRIN BETA7 CYTOPLASMIC TAIL PEPTIDE
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.
About this Structure
2BRQ is a Protein complex structure of sequences from Homo sapiens. 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 Mon Mar 31 02:10:46 2008
