| Structural highlights
Disease
[CO6A3_HUMAN] Defects in COL6A3 are a cause of Bethlem myopathy (BM) [MIM:158810]. BM is a rare autosomal dominant proximal myopathy characterized by early childhood onset (complete penetrance by the age of 5) and joint contractures most frequently affecting the elbows and ankles.[1] [2] [3] [4] [5] Defects in COL6A3 are a cause of Ullrich congenital muscular dystrophy (UCMD) [MIM:254090]; also known as Ullrich scleroatonic muscular dystrophy. UCMD is an autosomal recessive congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.[6] [7]
Function
[CO6A3_HUMAN] Collagen VI acts as a cell-binding protein.
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
The C-terminal Kunitz-type domain from the alpha 3 chain of human type VI collagen (C5), a single 58 amino acid residue chain with three disulfide bridges, was cloned, expressed and crystallized in a monoclonic form, space group P2(1), with a = 25.7 A, b = 38.2 A, c = 28.8 A and beta = 109 degrees. The structure was resolved by molecular replacement, using Alzheimer's protein precursor inhibitor and bovine pancreatic trypsin inhibitor three-dimensional structures as search models. The molecule with one sulfate ion and 43 associated water molecules was refined by XPLOR to an R-factor of 18.9% at 1.6 A. The molecule was not degraded by trypsin and did not inhibit trypsin or tested serine proteases. As opposed to the other Kunitz family members, C5 demonstrates left-handed chirality of the Cys14-Cys38 disulfide bond. Inversion of the Thr13 carbonyl and bulky side-chains at the interface with trypsin in a model of the C5-trypsin complex may explain the lack of inhibition of trypsin.
The 1.6 A structure of Kunitz-type domain from the alpha 3 chain of human type VI collagen.,Arnoux B, Merigeau K, Saludjian P, Norris F, Norris K, Bjorn S, Olsen O, Petersen L, Ducruix A J Mol Biol. 1995 Mar 10;246(5):609-17. PMID:7533217[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P. Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet. 2002 Jun;70(6):1446-58. Epub 2002 Apr 24. PMID:11992252 doi:S0002-9297(07)60697-1
- ↑ Pan TC, Zhang RZ, Pericak-Vance MA, Tandan R, Fries T, Stajich JM, Viles K, Vance JM, Chu ML, Speer MC. Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy. Hum Mol Genet. 1998 May;7(5):807-12. PMID:9536084
- ↑ Pepe G, Bertini E, Giusti B, Brunelli T, Comeglio P, Saitta B, Merlini L, Chu ML, Federici G, Abbate R. A novel de novo mutation in the triple helix of the COL6A3 gene in a two-generation Italian family affected by Bethlem myopathy. A diagnostic approach in the mutations' screening of type VI collagen. Neuromuscul Disord. 1999 Jun;9(4):264-71. PMID:10399756
- ↑ Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, Marie SK, Chu ML, Swoboda K, Muntoni F, Bonnemann CG, Flanigan KM, Bushby KM, Weiss RB. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet. 2005 Feb;42(2):108-20. PMID:15689448 doi:42/2/108
- ↑ Baker NL, Morgelin M, Pace RA, Peat RA, Adams NE, Gardner RJ, Rowland LP, Miller G, De Jonghe P, Ceulemans B, Hannibal MC, Edwards M, Thompson EM, Jacobson R, Quinlivan RC, Aftimos S, Kornberg AJ, North KN, Bateman JF, Lamande SR. Molecular consequences of dominant Bethlem myopathy collagen VI mutations. Ann Neurol. 2007 Oct;62(4):390-405. PMID:17886299 doi:10.1002/ana.21213
- ↑ Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P. Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet. 2002 Jun;70(6):1446-58. Epub 2002 Apr 24. PMID:11992252 doi:S0002-9297(07)60697-1
- ↑ Lampe AK, Dunn DM, von Niederhausern AC, Hamil C, Aoyagi A, Laval SH, Marie SK, Chu ML, Swoboda K, Muntoni F, Bonnemann CG, Flanigan KM, Bushby KM, Weiss RB. Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy. J Med Genet. 2005 Feb;42(2):108-20. PMID:15689448 doi:42/2/108
- ↑ Arnoux B, Merigeau K, Saludjian P, Norris F, Norris K, Bjorn S, Olsen O, Petersen L, Ducruix A. The 1.6 A structure of Kunitz-type domain from the alpha 3 chain of human type VI collagen. J Mol Biol. 1995 Mar 10;246(5):609-17. PMID:7533217
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