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Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops
The V3 loop of the glycoprotein 120 (gp120) is a contact point for cell entry of HIV-1 leading to infection. Despite sequence variability and lack of specific structure, the highly flexible V3 loop possesses a well-defined role in recognizing and selecting cell-bound coreceptors CCR5 and CXCR4 throu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501474/ https://www.ncbi.nlm.nih.gov/pubmed/23185486 http://dx.doi.org/10.1371/journal.pone.0049925 |
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author | López de Victoria, Aliana Tamamis, Phanourios Kieslich, Chris A. Morikis, Dimitrios |
author_facet | López de Victoria, Aliana Tamamis, Phanourios Kieslich, Chris A. Morikis, Dimitrios |
author_sort | López de Victoria, Aliana |
collection | PubMed |
description | The V3 loop of the glycoprotein 120 (gp120) is a contact point for cell entry of HIV-1 leading to infection. Despite sequence variability and lack of specific structure, the highly flexible V3 loop possesses a well-defined role in recognizing and selecting cell-bound coreceptors CCR5 and CXCR4 through a mechanism of charge complementarity. We have performed two independent molecular dynamics (MD) simulations to gain insights into the dynamic character of two V3 loops with slightly different sequences, but significantly different starting crystallographic structures. We have identified highly populated trajectory-specific salt bridges between oppositely charged stem residues Arg9 and Glu25 or Asp29. The two trajectories share nearly identical correlated motions within the simulations, despite their different overall structures. High occupancy salt bridges play a key role in the major cross-correlated motions in both trajectories, and may be responsible for transient structural stability in preparation for coreceptor binding. In addition, the two V3 loops visit conformations with similarities in spatial distributions of electrostatic potentials, despite their inherent flexibility, which may play a role in coreceptor recognition. It is plausible that cooperativity between overall electrostatic potential, charged residue interactions, and correlated motions could be associated with a coreceptor selection and binding. |
format | Online Article Text |
id | pubmed-3501474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35014742012-11-26 Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops López de Victoria, Aliana Tamamis, Phanourios Kieslich, Chris A. Morikis, Dimitrios PLoS One Research Article The V3 loop of the glycoprotein 120 (gp120) is a contact point for cell entry of HIV-1 leading to infection. Despite sequence variability and lack of specific structure, the highly flexible V3 loop possesses a well-defined role in recognizing and selecting cell-bound coreceptors CCR5 and CXCR4 through a mechanism of charge complementarity. We have performed two independent molecular dynamics (MD) simulations to gain insights into the dynamic character of two V3 loops with slightly different sequences, but significantly different starting crystallographic structures. We have identified highly populated trajectory-specific salt bridges between oppositely charged stem residues Arg9 and Glu25 or Asp29. The two trajectories share nearly identical correlated motions within the simulations, despite their different overall structures. High occupancy salt bridges play a key role in the major cross-correlated motions in both trajectories, and may be responsible for transient structural stability in preparation for coreceptor binding. In addition, the two V3 loops visit conformations with similarities in spatial distributions of electrostatic potentials, despite their inherent flexibility, which may play a role in coreceptor recognition. It is plausible that cooperativity between overall electrostatic potential, charged residue interactions, and correlated motions could be associated with a coreceptor selection and binding. Public Library of Science 2012-11-19 /pmc/articles/PMC3501474/ /pubmed/23185486 http://dx.doi.org/10.1371/journal.pone.0049925 Text en © 2012 López de Victoria 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 López de Victoria, Aliana Tamamis, Phanourios Kieslich, Chris A. Morikis, Dimitrios Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops |
title | Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops |
title_full | Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops |
title_fullStr | Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops |
title_full_unstemmed | Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops |
title_short | Insights into the Structure, Correlated Motions, and Electrostatic Properties of Two HIV-1 gp120 V3 Loops |
title_sort | insights into the structure, correlated motions, and electrostatic properties of two hiv-1 gp120 v3 loops |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501474/ https://www.ncbi.nlm.nih.gov/pubmed/23185486 http://dx.doi.org/10.1371/journal.pone.0049925 |
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