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2kdg

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Revision as of 10:18, 18 July 2018

Solution Structure of the 1st Ig domain of Myotilin

Structural highlights

2kdg is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	MYOT, TTID (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MYOTI_HUMAN] Defects in MYOT are the cause of limb-girdle muscular dystrophy type 1A (LGMD1A) [MIM:159000]. LGMD1A is an autosomal dominant degenerative myopathy with onset within a mean age of 28 years. LGMD1A is characterized by progressive skeletal muscle weakness of the hip and shoulder girdles, later progressing to include distal weakness, as well as a distinctive dysarthric pattern of speech. Affected muscle exhibits disorganization and streaming of the Z-line.^[1] ^[2] Defects in MYOT are the cause of myopathy myofibrillar type 3 (MFM3) [MIM:609200]. A neuromuscular disorder characterized by progressive skeletal muscle weakness greater distally than proximally, tight heel cords, hyporeflexia, cardiomyopathy and peripheral neuropathy in some patients. Affected muscle exhibits disorganization and streaming of the Z-line, presence of large hyaline structures, excessive accumulation of myotilin and other ectopically expressed proteins and prominent congophilic deposits.^[3] Defects in MYOT are the cause of spheroid body myopathy (SBM) [MIM:182920]. SBM is an autosomal dominant form of myofibrillar myopathy (MFM), characterized by slowly progressing proximal muscle weakness and dysarthric nasal speech. There is no evidence of cardiomyopathy. Muscle biopsy shows spheroid bodies within the type I muscle fibers.^[4]

Function

[MYOTI_HUMAN] Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells.^[5]

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

Myotilin is a 57 kDa actin-binding and -bundling protein that consists of a unique serine-rich amino-terminus, two Ig-domains and a short carboxy-terminus with a PDZ-binding motif. Myotilin localizes in sarcomeric Z-discs, where it interacts with several sarcomeric proteins. Point mutations in myotilin cause muscle disorders morphologically highlighted by sarcomeric disarray and aggregation. The actin-binding and dimerization propensity of myotilin has been mapped to the Ig-domains. Here we present high-resolution structure of the first Ig-domain of myotilin (MyoIg1) determined with solution state NMR spectroscopy. Nearly complete chemical shift assignments of MyoIg1 were achieved despite several missing backbone 1H-15N-HSQC signals. The structure derived from distance and dihedral angle restraints using torsion angle dynamics was further refined using molecular dynamics. The structure of MyoIg1 exhibits I-type Ig-fold. The absence of several backbone 1H-15N-HSQC signals can be explained by conformational exchange taking place at the hydrophobic core of the protein.

Solution structure of the first immunoglobulin domain of human myotilin.,Heikkinen O, Permi P, Koskela H, Carpen O, Ylanne J, Kilpelainen I J Biomol NMR. 2009 Jun;44(2):107-12. Epub 2009 May 6. PMID:19418025^[6]

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

References

↑ Hauser MA, Horrigan SK, Salmikangas P, Torian UM, Viles KD, Dancel R, Tim RW, Taivainen A, Bartoloni L, Gilchrist JM, Stajich JM, Gaskell PC, Gilbert JR, Vance JM, Pericak-Vance MA, Carpen O, Westbrook CA, Speer MC. Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet. 2000 Sep 1;9(14):2141-7. PMID:10958653
↑ Hauser MA, Conde CB, Kowaljow V, Zeppa G, Taratuto AL, Torian UM, Vance J, Pericak-Vance MA, Speer MC, Rosa AL. myotilin Mutation found in second pedigree with LGMD1A. Am J Hum Genet. 2002 Dec;71(6):1428-32. Epub 2002 Nov 11. PMID:12428213 doi:10.1086/344532
↑ Selcen D, Engel AG. Mutations in myotilin cause myofibrillar myopathy. Neurology. 2004 Apr 27;62(8):1363-71. PMID:15111675
↑ Foroud T, Pankratz N, Batchman AP, Pauciulo MW, Vidal R, Miravalle L, Goebel HH, Cushman LJ, Azzarelli B, Horak H, Farlow M, Nichols WC. A mutation in myotilin causes spheroid body myopathy. Neurology. 2005 Dec 27;65(12):1936-40. PMID:16380616 doi:10.1212/01.wnl.0000188872.28149.9a
↑ Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, Schroder R, Lappalainen P, Furst DO, Carpen O. Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly. Hum Mol Genet. 2003 Jan 15;12(2):189-203. PMID:12499399
↑ Heikkinen O, Permi P, Koskela H, Carpen O, Ylanne J, Kilpelainen I. Solution structure of the first immunoglobulin domain of human myotilin. J Biomol NMR. 2009 Jun;44(2):107-12. Epub 2009 May 6. PMID:19418025 doi:10.1007/s10858-009-9320-4

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/2kdg"

@@ Line 1: / Line 1: @@
 ==Solution Structure of the 1st Ig domain of Myotilin==
 <StructureSection load='2kdg' size='340' side='right' caption='[[2kdg]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2kdg]] is a 1 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=2KDG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KDG FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MYOT, TTID ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2kdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdg OCA], [http://pdbe.org/2kdg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kdg RCSB], [http://www.ebi.ac.uk/pdbsum/2kdg PDBsum]</span></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=2kdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdg OCA], [http://pdbe.org/2kdg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kdg RCSB], [http://www.ebi.ac.uk/pdbsum/2kdg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kdg ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kd/2kdg_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kd/2kdg_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kdg ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 45: / Line 46: @@
 [[Category: Actin-binding]]
 [[Category: Cell membrane]]
+[[Category: Cytoplasm]]
 [[Category: Cytoskeleton]]
 [[Category: Disease mutation]]
@@ Line 53: / Line 55: @@
 [[Category: Muscle protein]]
 [[Category: Myotilin]]
+[[Category: Polymorphism]]
 [[Category: Structural protein]]

2kdg

From Proteopedia

Revision as of 10:18, 18 July 2018

Solution Structure of the 1st Ig domain of Myotilin

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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