2j3s
From Proteopedia
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|PDB= 2j3s |SIZE=350|CAPTION= <scene name='initialview01'>2j3s</scene>, resolution 2.50Å | |PDB= 2j3s |SIZE=350|CAPTION= <scene name='initialview01'>2j3s</scene>, resolution 2.50Å | ||
|SITE= <scene name='pdbsite=AC1:Br+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Dio+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Dio+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Br+Binding+Site+For+Chain+B'>AC4</scene>, <scene name='pdbsite=AC5:Dio+Binding+Site+For+Chain+B'>AC5</scene> and <scene name='pdbsite=AC6:Dio+Binding+Site+For+Chain+B'>AC6</scene> | |SITE= <scene name='pdbsite=AC1:Br+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Dio+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Dio+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Br+Binding+Site+For+Chain+B'>AC4</scene>, <scene name='pdbsite=AC5:Dio+Binding+Site+For+Chain+B'>AC5</scene> and <scene name='pdbsite=AC6:Dio+Binding+Site+For+Chain+B'>AC6</scene> | ||
| - | |LIGAND= <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene> | + | |LIGAND= <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2bp3|2BP3]], [[2jf1|2JF1]], [[2aav|2AAV]], [[2brq|2BRQ]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j3s OCA], [http://www.ebi.ac.uk/pdbsum/2j3s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2j3s RCSB]</span> | ||
}} | }} | ||
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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== | ||
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[[Category: Kiema, T R.]] | [[Category: Kiema, T R.]] | ||
[[Category: Ylanne, J.]] | [[Category: Ylanne, J.]] | ||
| - | [[Category: BR]] | ||
| - | [[Category: DIO]] | ||
| - | [[Category: GOL]] | ||
[[Category: acetylation]] | [[Category: acetylation]] | ||
[[Category: actin-binding]] | [[Category: actin-binding]] | ||
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[[Category: structural protein]] | [[Category: structural protein]] | ||
| - | ''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 03:52:29 2008'' |
Revision as of 00:52, 31 March 2008
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| , resolution 2.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , and | ||||||
| Ligands: | , , | ||||||
| Related: | 2BP3, 2JF1, 2AAV, 2BRQ
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Mon Mar 31 03:52:29 2008
