2MQ3

NMR structure of the c3 domain of human cardiac myosin binding protein-c with a hypertrophic cardiomyopathy-related mutation R502W.

Summary for 2MQ3

• Entry DOI: 10.2210/pdb2mq3/pdb
• Related: 2mq0
• NMR Information: BMRB: 25010
• Descriptor: Myosin-binding protein C, cardiac-type (1 entity in total)
• Functional Keywords: cardiac myosin binding protein c, c3 domain, ig-like, hypertrophic cardiomyopathy, contractile protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 10856.34

Authors

Zhang, X.,De, S.,Mcintosh, L.P.,Paetzel, M. (deposition date: 2014-06-12, release date: 2014-07-30, Last modification date: 2024-05-15)

Primary citation

Zhang, X.L.,De, S.,McIntosh, L.P.,Paetzel, M.
Structural Characterization of the C3 Domain of Cardiac Myosin Binding Protein C and Its Hypertrophic Cardiomyopathy-Related R502W Mutant.
Biochemistry, 53:5332-5342, 2014

PubMed Abstract: Human cardiac myosin binding protein C (cMyBP-C), a thick filament protein found within the sarcomere of cardiac muscle, regulates muscle contraction and is essential for proper muscle function. Hypertrophic cardiomyopathy (HCM), a genetic disease affecting 1 in 500 people, is the major cause of death in young athletes. It is caused by genetic mutations within sarcomeric proteins. Forty-two percent of the HCM-related mutations are found in cMyBP-C. Here we present the nuclear magnetic resonance-derived structural ensembles of the wild-type cMyBP-C C3 domain and its HCM-related R502W mutant. The C3 domain adopts an immunoglobulin-like fold, and mutation of the exposed Arg502 to a tryptophan does not perturb its structure, dynamics, or stability. However, the R502W mutation does alter the predicted electrostatic properties of the C3 domain. We hypothesize that this mutation, and other HCM-linked mutations found within the same domain, may directly disrupt the interaction of cMyBP-C with other sarcomeric proteins.

PubMed: 25058872
DOI: 10.1021/bi500784g

Experimental method

SOLUTION NMR