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Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties
BACKGROUND: The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295656/ https://www.ncbi.nlm.nih.gov/pubmed/22313935 http://dx.doi.org/10.1186/2046-1682-5-3 |
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author | López de Victoria, Aliana Kieslich, Chris A Rizos, Apostolos K Krambovitis, Elias Morikis, Dimitrios |
author_facet | López de Victoria, Aliana Kieslich, Chris A Rizos, Apostolos K Krambovitis, Elias Morikis, Dimitrios |
author_sort | López de Victoria, Aliana |
collection | PubMed |
description | BACKGROUND: The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes. RESULTS: Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N(6)X(7)T(8)|S(8)X(9 )sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution. CONCLUSIONS: We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3 loop with coreceptors CCR5/CXCR4, whereas the charge distribution contributes to the specific short-range interactions responsible for the formation of the bound complex. We also propose a scheme for coreceptor selectivity based on the sequence glycosylation motif, the 11/24/25 rule, and net charge. |
format | Online Article Text |
id | pubmed-3295656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32956562012-03-08 Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties López de Victoria, Aliana Kieslich, Chris A Rizos, Apostolos K Krambovitis, Elias Morikis, Dimitrios BMC Biophys Research Article BACKGROUND: The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes. RESULTS: Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N(6)X(7)T(8)|S(8)X(9 )sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution. CONCLUSIONS: We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3 loop with coreceptors CCR5/CXCR4, whereas the charge distribution contributes to the specific short-range interactions responsible for the formation of the bound complex. We also propose a scheme for coreceptor selectivity based on the sequence glycosylation motif, the 11/24/25 rule, and net charge. BioMed Central 2012-02-07 /pmc/articles/PMC3295656/ /pubmed/22313935 http://dx.doi.org/10.1186/2046-1682-5-3 Text en Copyright ©2012 de Victoria et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article López de Victoria, Aliana Kieslich, Chris A Rizos, Apostolos K Krambovitis, Elias Morikis, Dimitrios Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties |
title | Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties |
title_full | Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties |
title_fullStr | Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties |
title_full_unstemmed | Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties |
title_short | Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties |
title_sort | clustering of hiv-1 subtypes based on gp120 v3 loop electrostatic properties |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295656/ https://www.ncbi.nlm.nih.gov/pubmed/22313935 http://dx.doi.org/10.1186/2046-1682-5-3 |
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