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Disorder in Cholesterol-Binding Functionality of CRAC Peptides: A Molecular Dynamics Study
[Image: see text] The cholesterol recognition/interaction amino acid consensus (CRAC) motif is a primary structure pattern used to identify regions that may be responsible for preferential cholesterol binding in many proteins. The leukotoxin LtxA, which is produced by a pathogenic bacterium, contain...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242004/ https://www.ncbi.nlm.nih.gov/pubmed/25347282 http://dx.doi.org/10.1021/jp5106423 |
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author | Miller, Cayla M. Brown, Angela C. Mittal, Jeetain |
author_facet | Miller, Cayla M. Brown, Angela C. Mittal, Jeetain |
author_sort | Miller, Cayla M. |
collection | PubMed |
description | [Image: see text] The cholesterol recognition/interaction amino acid consensus (CRAC) motif is a primary structure pattern used to identify regions that may be responsible for preferential cholesterol binding in many proteins. The leukotoxin LtxA, which is produced by a pathogenic bacterium, contains two CRAC seqences, only one of which is responsible for cholesterol binding, and the binding is required for cytotoxicity. The factors, in addition to the CRAC definition, that may be responsible for cholesterol-binding functionality and atomistic interactions between the CRAC region and cholesterol are as yet unknown. This study uses molecular dynamics simulations to identify structural characteristics and specific interactions of the two LtxA CRAC peptides with both pure phospholipid and binary cholesterol–phospholipid bilayers. We have identified changes in the secondary structure of these peptides that occur upon cholesterol binding, which are not seen when it is associated with a cholesterol-devoid membrane, and which show salient coupling of structural disorder and function. Additionally, the central tyrosine residue of the CRAC motif was found to play a significant role in cholesterol binding, though residues outside of the CRAC motif also influence membrane interactions and functionality of the CRAC region. |
format | Online Article Text |
id | pubmed-4242004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-42420042015-10-27 Disorder in Cholesterol-Binding Functionality of CRAC Peptides: A Molecular Dynamics Study Miller, Cayla M. Brown, Angela C. Mittal, Jeetain J Phys Chem B [Image: see text] The cholesterol recognition/interaction amino acid consensus (CRAC) motif is a primary structure pattern used to identify regions that may be responsible for preferential cholesterol binding in many proteins. The leukotoxin LtxA, which is produced by a pathogenic bacterium, contains two CRAC seqences, only one of which is responsible for cholesterol binding, and the binding is required for cytotoxicity. The factors, in addition to the CRAC definition, that may be responsible for cholesterol-binding functionality and atomistic interactions between the CRAC region and cholesterol are as yet unknown. This study uses molecular dynamics simulations to identify structural characteristics and specific interactions of the two LtxA CRAC peptides with both pure phospholipid and binary cholesterol–phospholipid bilayers. We have identified changes in the secondary structure of these peptides that occur upon cholesterol binding, which are not seen when it is associated with a cholesterol-devoid membrane, and which show salient coupling of structural disorder and function. Additionally, the central tyrosine residue of the CRAC motif was found to play a significant role in cholesterol binding, though residues outside of the CRAC motif also influence membrane interactions and functionality of the CRAC region. American Chemical Society 2014-10-27 2014-11-20 /pmc/articles/PMC4242004/ /pubmed/25347282 http://dx.doi.org/10.1021/jp5106423 Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Miller, Cayla M. Brown, Angela C. Mittal, Jeetain Disorder in Cholesterol-Binding Functionality of CRAC Peptides: A Molecular Dynamics Study |
title | Disorder
in Cholesterol-Binding Functionality of CRAC
Peptides: A Molecular Dynamics Study |
title_full | Disorder
in Cholesterol-Binding Functionality of CRAC
Peptides: A Molecular Dynamics Study |
title_fullStr | Disorder
in Cholesterol-Binding Functionality of CRAC
Peptides: A Molecular Dynamics Study |
title_full_unstemmed | Disorder
in Cholesterol-Binding Functionality of CRAC
Peptides: A Molecular Dynamics Study |
title_short | Disorder
in Cholesterol-Binding Functionality of CRAC
Peptides: A Molecular Dynamics Study |
title_sort | disorder
in cholesterol-binding functionality of crac
peptides: a molecular dynamics study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242004/ https://www.ncbi.nlm.nih.gov/pubmed/25347282 http://dx.doi.org/10.1021/jp5106423 |
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