title: Crystal structure of the C1 domain of cardiac myosin binding protein-C: implications for hypertrophic cardiomyopathy.
abstract: C-protein is a major component of skeletal and cardiac muscle thick filaments. Mutations in the gene encoding cardiac C-protein [cardiac myosin binding protein-C (cMyBP-C)] are one of the principal causes of hypertrophic cardiomyopathy. cMyBP-C is a string of globular domains including eight immunoglobulin-like and three fibronectin-like domains termed C0-C10. It binds to myosin and titin, and probably to actin, and may have both a structural and a regulatory role in muscle function. To help to understand the pathology of the known mutations, we have solved the structure of the immunoglobulin-like C1 domain of MyBP-C by X-ray crystallography to a resolution of 1.55 A. Mutations associated with hypertrophic cardiomyopathy are clustered at one end towards the C-terminus, close to the important C1C2 linker, where they alter the structural integrity of this region and its interactions.
authors: Biomolecular Medicine Department, SORA Division, Imperial College London, London SW7 2AZ, UK.
authors: Lata
authors: L
authors: Govada
authors: Liz
authors: L
authors: Carpenter
authors: Paula C A
authors: PC
authors: da Fonseca
authors: John R
authors: JR
authors: Helliwell
authors: Pierre
authors: P
authors: Rizkallah
authors: Emily
authors: E
authors: Flashman
authors: Naomi E
authors: NE
authors: Chayen
authors: Charles
authors: C
authors: Redwood
authors: John M
authors: JM
authors: Squire
mesh_terms: D000595:Amino Acid Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C