Crystal structure of the C1 domain of cardiac myosin binding protein-C: implications for hypertrophic cardiomyopathy.
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.
Govada
Lata
L
Biomolecular Medicine Department, SORA Division, Imperial College London, London SW7 2AZ, UK.
Carpenter
Liz
L
da Fonseca
Paula C A
PC
Helliwell
John R
JR
Rizkallah
Pierre
P
Flashman
Emily
E
Chayen
Naomi E
NE
Redwood
Charles
C
Squire
John M
JM
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
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C