1v05

From Proteopedia

(Difference between revisions)

Current revision

Dimerization of human Filamin C: crystal structure of the domain 24

Structural highlights

1v05 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.43Å
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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Filamins are essential in cell motility and many developmental processes. They are large actin cross linking proteins that contain actin binding domains in their N termini and a long rod region constructed from 24 tandem Ig domains. Dimerization is crucial for the actin crosslinking function of filamins and requires the most C-terminal Ig domain. We describe here the crystal structure of this 24th Ig domain (Ig24) of human filamin C and show how it mediates dimerization. The dimer interface is novel and quite different to that seen in the Dictyostelium discoideum filamin analog. The sequence signature of the dimerization interface suggests that the C-terminal domains of all vertebrate filamins share the same dimerization mechanism. Furthermore, we show that point mutations in the dimerization interface disrupt the dimer and that the dissociation constant for recombinant Ig24 is in the micromolar range.

Structural basis for vertebrate filamin dimerization.,Pudas R, Kiema TR, Butler PJ, Stewart M, Ylanne J Structure. 2005 Jan;13(1):111-9. PMID:15642266^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ Pudas R, Kiema TR, Butler PJ, Stewart M, Ylanne J. Structural basis for vertebrate filamin dimerization. Structure. 2005 Jan;13(1):111-9. PMID:15642266 doi:10.1016/j.str.2004.10.014

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1v05"

@@ Line 3: / Line 3: @@
 <StructureSection load='1v05' size='340' side='right'caption='[[1v05]], [[Resolution|resolution]] 1.43&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1v05]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V05 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1v05]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V05 FirstGlance]. <br>
-</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=1v05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v05 OCA], [https://pdbe.org/1v05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v05 RCSB], [https://www.ebi.ac.uk/pdbsum/1v05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v05 ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43&#8491;</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=1v05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v05 OCA], [https://pdbe.org/1v05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v05 RCSB], [https://www.ebi.ac.uk/pdbsum/1v05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v05 ProSAT]</span></td></tr>
 </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 ==
+[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.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 38: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Kiema, T R]]
+[[Category: Kiema T-R]]
-[[Category: Pudas, R]]
+[[Category: Pudas R]]
-[[Category: Ylanne, J]]
+[[Category: Ylanne J]]
-[[Category: Actin-binding protein]]
-[[Category: Immunoglobulin]]
 [[Category: Z-disk]]

1v05

From Proteopedia

Current revision

Dimerization of human Filamin C: crystal structure of the domain 24

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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