2j3s
From Proteopedia
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| - | [[Image:2j3s.gif|left|200px]]<br /><applet load="2j3s" size=" | + | [[Image:2j3s.gif|left|200px]]<br /><applet load="2j3s" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2j3s, resolution 2.50Å" /> | caption="2j3s, resolution 2.50Å" /> | ||
'''CRYSTAL STRUCTURE OF THE HUMAN FILAMIN A IG DOMAINS 19 TO 21'''<br /> | '''CRYSTAL STRUCTURE OF THE HUMAN FILAMIN A IG DOMAINS 19 TO 21'''<br /> | ||
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==Overview== | ==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. | 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. | ||
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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== | ||
| - | 2J3S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BR, DIO and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:Dio Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http:// | + | 2J3S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BR:'>BR</scene>, <scene name='pdbligand=DIO:'>DIO</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:Dio Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J3S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: structural protein]] | [[Category: structural protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:52:23 2008'' |
Revision as of 10:52, 23 January 2008
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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 with , and as ligands. Known structural/functional Site: . 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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