Cargando…
Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602012/ https://www.ncbi.nlm.nih.gov/pubmed/23527136 http://dx.doi.org/10.1371/journal.pone.0059206 |
_version_ | 1782263516482240512 |
---|---|
author | Gajendrarao, Poornima Krishnamoorthy, Navaneethakrishnan Kassem, Heba Sh Moharem-Elgamal, Sarah Cecchi, Franco Olivotto, Iacopo Yacoub, Magdi H. |
author_facet | Gajendrarao, Poornima Krishnamoorthy, Navaneethakrishnan Kassem, Heba Sh Moharem-Elgamal, Sarah Cecchi, Franco Olivotto, Iacopo Yacoub, Magdi H. |
author_sort | Gajendrarao, Poornima |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3602012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36020122013-03-22 Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C Gajendrarao, Poornima Krishnamoorthy, Navaneethakrishnan Kassem, Heba Sh Moharem-Elgamal, Sarah Cecchi, Franco Olivotto, Iacopo Yacoub, Magdi H. PLoS One Research Article 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. Public Library of Science 2013-03-19 /pmc/articles/PMC3602012/ /pubmed/23527136 http://dx.doi.org/10.1371/journal.pone.0059206 Text en © 2013 Gajendrarao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gajendrarao, Poornima Krishnamoorthy, Navaneethakrishnan Kassem, Heba Sh Moharem-Elgamal, Sarah Cecchi, Franco Olivotto, Iacopo Yacoub, Magdi H. Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C |
title | Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C |
title_full | Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C |
title_fullStr | Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C |
title_full_unstemmed | Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C |
title_short | Molecular Modeling of Disease Causing Mutations in Domain C1 of cMyBP-C |
title_sort | molecular modeling of disease causing mutations in domain c1 of cmybp-c |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602012/ https://www.ncbi.nlm.nih.gov/pubmed/23527136 http://dx.doi.org/10.1371/journal.pone.0059206 |
work_keys_str_mv | AT gajendraraopoornima molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc AT krishnamoorthynavaneethakrishnan molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc AT kassemhebash molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc AT moharemelgamalsarah molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc AT cecchifranco molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc AT olivottoiacopo molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc AT yacoubmagdih molecularmodelingofdiseasecausingmutationsindomainc1ofcmybpc |