2brq: Difference between revisions
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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. | ||
==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== | ||
2BRQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GSW:'>GSW</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRQ OCA]. | 2BRQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=GSW:'>GSW</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRQ OCA]. | ||
==Reference== | ==Reference== | ||
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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 Sun Feb 3 10:27:11 2008'' | ||
