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Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C
- Source :
- PLoS ONE, Vol 8, Iss 3, p e59206 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science, 2013.
-
Abstract
- Cardiac myosin binding protein-C (cMyBP-C) is a multi-domain (C0-C10) protein that regulates heart muscle contraction through interaction with myosin, actin and other sarcomeric proteins. Several mutations of this protein cause familial hypertrophic cardiomyopathy (HCM). Domain C1 of cMyBP-C plays a central role in protein interactions with actin and myosin. Here, we studied structure-function relationship of three disease causing mutations, Arg177His, Ala216Thr and Glu258Lys of the domain C1 using computational biology techniques with its available X-ray crystal structure. The results suggest that each mutation could affect structural properties of the domain C1, and hence it's structural integrity through modifying intra-molecular arrangements in a distinct mode. The mutations also change surface charge distributions, which could impact the binding of C1 with other sarcomeric proteins thereby affecting contractile function. These structural consequences of the C1 mutants could be valuable to understand the molecular mechanisms for the disease.
- Subjects :
- DYNAMICS
Models, Molecular
Mutant
DNA Mutational Analysis
lcsh:Medicine
Bioinformatics
Cardiovascular
Crystallography, X-Ray
FAMILIAL HYPERTROPHIC CARDIOMYOPATHY
Protein structure
MYOSIN-BINDING
CONTRACTION
Myosin
THICK FILAMENTS
Macromolecular Structure Analysis
lcsh:Science
PHOSPHORYLATION
Cardiomyopathy, Hypertrophic, Familial
Carrier Proteins
Computational Biology
Egypt
Humans
Molecular Dynamics Simulation
Mutation, Missense
Static Electricity
Protein Structure, Tertiary
Multidisciplinary
Crystallography
MUSCLE
Cell biology
Myosin binding
Medicine
Science & Technology - Other Topics
Cardiomyopathies
REGULATOR
Research Article
Protein Structure
General Science & Technology
Protein domain
Materials Science
GENETIC-BASIS
Biophysics
macromolecular substances
Biology
Protein–protein interaction
Motor protein
MD Multidisciplinary
Actin
Heart Failure
Science & Technology
MULTIDISCIPLINARY SCIENCES
lcsh:R
BINDING-PROTEIN-C
lcsh:Q
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, Vol 8, Iss 3, p e59206 (2013), PLoS ONE
- Accession number :
- edsair.doi.dedup.....28dbcdea9da6318e49f497cddfcdce6a