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Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core
Polar residues lying between adjacent α-helical chains of coiled-coils often contribute to coiled-coil curvature and flexibility, while more typical core hydrophobic residues anneal the chains together. In tropomyosins, ranging from smooth and skeletal muscle to cytoplasmic isoforms, a highly conser...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Landes Bioscience
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384579/ https://www.ncbi.nlm.nih.gov/pubmed/22754618 http://dx.doi.org/10.4161/bioa.18117 |
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author | Moore, Jeffrey R. Li, Xiaochuan Nirody, Jasmine Fischer, Stefan Lehman, William |
author_facet | Moore, Jeffrey R. Li, Xiaochuan Nirody, Jasmine Fischer, Stefan Lehman, William |
author_sort | Moore, Jeffrey R. |
collection | PubMed |
description | Polar residues lying between adjacent α-helical chains of coiled-coils often contribute to coiled-coil curvature and flexibility, while more typical core hydrophobic residues anneal the chains together. In tropomyosins, ranging from smooth and skeletal muscle to cytoplasmic isoforms, a highly conserved Asp at residue 137 places negative charges within the tropomyosin coiled-coil core in a position which may affect the conformation needed for tropomyosin binding and regulatory movements on actin. Proteolytic susceptibility suggested that substituting a canonical Leu for the naturally occurring Asp at residue 137 increases inter-chain rigidity by stabilizing the tropomyosin coiled-coil. Using molecular dynamics, we now directly assess changes in coiled-coil curvature and flexibility caused by such mutants. Although the coiled-coil flexibility is modestly diminished near the residue 137 mutation site, as expected, a delocalized increase in flexibility along the overall coiled-coil is observed. Even though the average shape of the D137L tropomyosin is straighter than that of wild-type tropomyosin, it is still capable of binding actin due to this increase in flexibility. We conclude that the conserved, non-canonical Asp-137 destabilizes the local structure resulting in a local flexible region in the middle of tropomyosin that normally is important for tropomyosin steady-state equilibrium position on actin. |
format | Online Article Text |
id | pubmed-3384579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-33845792012-06-29 Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core Moore, Jeffrey R. Li, Xiaochuan Nirody, Jasmine Fischer, Stefan Lehman, William Bioarchitecture Research Paper Polar residues lying between adjacent α-helical chains of coiled-coils often contribute to coiled-coil curvature and flexibility, while more typical core hydrophobic residues anneal the chains together. In tropomyosins, ranging from smooth and skeletal muscle to cytoplasmic isoforms, a highly conserved Asp at residue 137 places negative charges within the tropomyosin coiled-coil core in a position which may affect the conformation needed for tropomyosin binding and regulatory movements on actin. Proteolytic susceptibility suggested that substituting a canonical Leu for the naturally occurring Asp at residue 137 increases inter-chain rigidity by stabilizing the tropomyosin coiled-coil. Using molecular dynamics, we now directly assess changes in coiled-coil curvature and flexibility caused by such mutants. Although the coiled-coil flexibility is modestly diminished near the residue 137 mutation site, as expected, a delocalized increase in flexibility along the overall coiled-coil is observed. Even though the average shape of the D137L tropomyosin is straighter than that of wild-type tropomyosin, it is still capable of binding actin due to this increase in flexibility. We conclude that the conserved, non-canonical Asp-137 destabilizes the local structure resulting in a local flexible region in the middle of tropomyosin that normally is important for tropomyosin steady-state equilibrium position on actin. Landes Bioscience 2011-09-01 /pmc/articles/PMC3384579/ /pubmed/22754618 http://dx.doi.org/10.4161/bioa.18117 Text en Copyright © 2011 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Research Paper Moore, Jeffrey R. Li, Xiaochuan Nirody, Jasmine Fischer, Stefan Lehman, William Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
title | Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
title_full | Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
title_fullStr | Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
title_full_unstemmed | Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
title_short | Structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
title_sort | structural implications of conserved aspartate residues located in tropomyosin’s coiled-coil core |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384579/ https://www.ncbi.nlm.nih.gov/pubmed/22754618 http://dx.doi.org/10.4161/bioa.18117 |
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