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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C
PLoS ONE, Volume 8, No. 3, Article e59206, Year 2013
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Description
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. © 2013 Gajendrarao et al.
Authors & Co-Authors
Gajendrarao, Poornima
Qatar, Doha
Qatar Cardiovascular Research Center
Krishnamoorthy, Navaneethakrishnan
Qatar, Doha
Qatar Cardiovascular Research Center
Kassem, Heba Sh
Egypt
Ba-hcm National Programme at Aswan Heart Centre
Egypt, Alexandria
Faculty of Medicine
Moharem-Elgamal, Sarah
Egypt
Ba-hcm National Programme at Aswan Heart Centre
Egypt, Giza
National Heart Institute
Cecchi, Franco
Italy, Florence
Azienda Ospedaliera Careggi
Olivotto, Iacopo
Italy, Florence
Azienda Ospedaliera Careggi
Yacoub, Magdi H.
Qatar, Doha
Qatar Cardiovascular Research Center
Egypt
Ba-hcm National Programme at Aswan Heart Centre
United Kingdom, London
National Heart and Lung Institute
Statistics
Citations: 21
Authors: 7
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0059206
e-ISSN:
19326203
Research Areas
Cancer
Noncommunicable Diseases