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==Solution NMR structure of the Filamin-migfilin complex==
==Solution NMR structure of the Filamin-migfilin complex==
<StructureSection load='2k9u' size='340' side='right' caption='[[2k9u]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2k9u' size='340' side='right'caption='[[2k9u]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2k9u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K9U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K9U FirstGlance]. <br>
<table><tr><td colspan='2'>[[2k9u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K9U FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k9u OCA], [http://pdbe.org/2k9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k9u RCSB], [http://www.ebi.ac.uk/pdbsum/2k9u PDBsum]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k9u OCA], [https://pdbe.org/2k9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k9u RCSB], [https://www.ebi.ac.uk/pdbsum/2k9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k9u ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FLNC_HUMAN FLNC_HUMAN] Defects in FLNC are the cause of myopathy myofibrillar type 5 (MFM5) [MIM:[https://omim.org/entry/609524 609524]. A neuromuscular disorder, usually with an adult onset, characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations, and clinical features of a limb-girdle myopathy.<ref>PMID:15929027</ref>  Defects in FLNC are the cause of myopathy distal type 4 (MPD4) [MIM:[https://omim.org/entry/614065 614065]. MPD4 is a slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation.<ref>PMID:21620354</ref>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/FBLI1_HUMAN FBLI1_HUMAN]] Serves as an anchoring site for cell-ECM adhesion proteins and filamin-containing actin filaments. Is implicated in cell shape modulation (spreading) and motility. May participate in the regulation of filamin-mediated cross-linking and stabilization of actin filaments. May also regulate the assembly of filamin-containing signaling complexes that control actin assembly. Promotes dissociation of FLNA from ITGB3 and ITGB7. Promotes activation of integrins and regulates integrin-mediated cell-cell adhesion.<ref>PMID:12679033</ref> <ref>PMID:12496242</ref> <ref>PMID:18829455</ref> <ref>PMID:19074766</ref> 
[https://www.uniprot.org/uniprot/FLNC_HUMAN FLNC_HUMAN] Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The linkage of heterodimeric (alpha/beta) integrin receptors with their extracellular matrix ligands and intracellular actin cytoskeleton is a fundamental step for controlling cell adhesion and migration. Binding of the actin-linking protein, talin, to integrin beta cytoplasmic tails (CTs) induces high affinity ligand binding (integrin activation), whereas binding of another actin-linking protein, filamin, to the integrin beta CTs negatively regulates this process by blocking the talin-integrin interaction. Here we show structurally that migfilin, a novel cytoskeletal adaptor highly enriched in the integrin adhesion sites, strongly interacts with the same region in filamin where integrin beta CTs bind. We further demonstrate that the migfilin interaction dissociates filamin from integrin and promotes the talin/integrin binding and integrin activation. Migfilin thus acts as a molecular switch to disconnect filamin from integrin for regulating integrin activation and dynamics of extracellular matrix-actin linkage.
 
Migfilin, a molecular switch in regulation of integrin activation.,Ithychanda SS, Das M, Ma YQ, Ding K, Wang X, Gupta S, Wu C, Plow EF, Qin J J Biol Chem. 2009 Feb 13;284(7):4713-22. doi: 10.1074/jbc.M807719200. Epub 2008, Dec 13. PMID:19074766<ref>PMID:19074766</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2k9u" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Filamin|Filamin]]
*[[Filamin 3D structures|Filamin 3D structures]]
*[[User:Georg Mlynek/workbench|User:Georg Mlynek/workbench]]
*[[User:Georg Mlynek/workbench|User:Georg Mlynek/workbench]]
== References ==
== References ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Ithychanda, S N]]
[[Category: Large Structures]]
[[Category: Qin, J]]
[[Category: Ithychanda SN]]
[[Category: Cell adhesion]]
[[Category: Qin J]]
[[Category: Cell junction]]
[[Category: Cell shape]]
[[Category: Cytoskeletal complex]]
[[Category: Cytoskeleton]]
[[Category: Lim domain]]
[[Category: Metal-binding]]
[[Category: Structural protein]]

Latest revision as of 09:44, 1 May 2024

Solution NMR structure of the Filamin-migfilin complexSolution NMR structure of the Filamin-migfilin complex

Structural highlights

2k9u is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FLNC_HUMAN Defects in FLNC are the cause of myopathy myofibrillar type 5 (MFM5) [MIM:609524. A neuromuscular disorder, usually with an adult onset, characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations, and clinical features of a limb-girdle myopathy.[1] Defects in FLNC are the cause of myopathy distal type 4 (MPD4) [MIM:614065. MPD4 is a slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation.[2]

Function

FLNC_HUMAN Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross-linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.

See Also

References

  1. ↑ Vorgerd M, van der Ven PF, Bruchertseifer V, Lowe T, Kley RA, Schroder R, Lochmuller H, Himmel M, Koehler K, Furst DO, Huebner A. A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy. Am J Hum Genet. 2005 Aug;77(2):297-304. Epub 2005 May 31. PMID:15929027 doi:10.1086/431959
  2. ↑ Duff RM, Tay V, Hackman P, Ravenscroft G, McLean C, Kennedy P, Steinbach A, Schoffler W, van der Ven PF, Furst DO, Song J, Djinovic-Carugo K, Penttila S, Raheem O, Reardon K, Malandrini A, Gambelli S, Villanova M, Nowak KJ, Williams DR, Landers JE, Brown RH Jr, Udd B, Laing NG. Mutations in the N-terminal actin-binding domain of filamin C cause a distal myopathy. Am J Hum Genet. 2011 Jun 10;88(6):729-40. Epub 2011 May 27. PMID:21620354 doi:10.1016/j.ajhg.2011.04.021
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