PDBsum entry 2mq3

Contractile protein

PDB id: 2mq3

Contents

Protein chain

95 a.a.

PDB id:

2mq3

Name:

Contractile protein

Title:

Nmr structure of the c3 domain of human cardiac myosin binding protein-c with a hypertrophic cardiomyopathy-related mutation r502w.

Structure:

Myosin-binding protein c, cardiac-type. Chain: a. Fragment: unp residues 453-543. Synonym: cardiac mybp-c, c-protein, cardiac muscle isoform. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mybpc3. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

X.Zhang,S.De,L.P.Mcintosh,M.Paetzel

Key ref:

X.L.Zhang et al. (2014). Structural characterization of the C3 domain of cardiac myosin binding protein C and its hypertrophic cardiomyopathy-related R502W mutant. Biochemistry, 53, 5332-5342. PubMed id: 25058872 DOI: 10.1021/bi500784g

Date:

12-Jun-14 Release date: 30-Jul-14

Protein chain

Q14896  (MYPC3_HUMAN) -  Myosin-binding protein C, cardiac-type from Homo sapiens

Seq: 1274 a.a.

Struc: 95 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1021/bi500784g

Biochemistry 53:5332-5342 (2014)

PubMed id: 25058872

Structural characterization of the C3 domain of cardiac myosin binding protein C and its hypertrophic cardiomyopathy-related R502W mutant.

X.L.Zhang, S.De, L.P.McIntosh, M.Paetzel.

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.