2j3s

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[[Image:2j3s.gif|left|200px]]<br /><applet load="2j3s" size="450" color="white" frame="true" align="right" spinBox="true"
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[[Image:2j3s.gif|left|200px]]<br /><applet load="2j3s" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2j3s, resolution 2.50&Aring;" />
caption="2j3s, resolution 2.50&Aring;" />
'''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==
 
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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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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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J3S OCA].
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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]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:47:21 2007''
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''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


2j3s, resolution 2.50Å

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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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