Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins

HIV type 1 (HIV-1) is characterized by its rapid genetic evolution, leading to challenges in anti-HIV therapy. However, the sequence variations in HIV-1 proteins are not randomly distributed due to a combination of functional constraints and genetic drift. In this study, we examined patterns of sequ...

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Main Authors:	Zhao, Yuqi, Wang, Yanjie, Gao, Yuedong, Li, Gonghua, Huang, Jingfei
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324911/

id	pubmed-4324911
recordtype	oai_dc
spelling	pubmed-43249112015-02-18 Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins Zhao, Yuqi Wang, Yanjie Gao, Yuedong Li, Gonghua Huang, Jingfei Research Article HIV type 1 (HIV-1) is characterized by its rapid genetic evolution, leading to challenges in anti-HIV therapy. However, the sequence variations in HIV-1 proteins are not randomly distributed due to a combination of functional constraints and genetic drift. In this study, we examined patterns of sequence variability for evidence of linked sequence changes (termed as coevolution or covariation) in 15 HIV-1 proteins. It shows that the percentage of charged residues in the coevolving residues is significantly higher than that in all the HIV-1 proteins. Most of the coevolving residues are spatially proximal in the protein structures and tend to form relatively compact and independent units in the tertiary structures, termed as “protein sectors”. These protein sectors are closely associated with anti-HIV drug resistance, T cell epitopes, and antibody binding sites. Finally, we explored candidate peptide inhibitors based on the protein sectors. Our results can establish an association between the coevolving residues and molecular functions of HIV-1 proteins, and then provide us with valuable knowledge of pathology of HIV-1 and therapeutics development. Public Library of Science 2015-02-11 /pmc/articles/PMC4324911/ /pubmed/25671429 http://dx.doi.org/10.1371/journal.pone.0117506 Text en © 2015 Zhao 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhao, Yuqi Wang, Yanjie Gao, Yuedong Li, Gonghua Huang, Jingfei
spellingShingle	Zhao, Yuqi Wang, Yanjie Gao, Yuedong Li, Gonghua Huang, Jingfei Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins
author_facet	Zhao, Yuqi Wang, Yanjie Gao, Yuedong Li, Gonghua Huang, Jingfei
author_sort	Zhao, Yuqi
title	Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins
title_short	Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins
title_full	Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins
title_fullStr	Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins
title_full_unstemmed	Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins
title_sort	integrated analysis of residue coevolution and protein structures capture key protein sectors in hiv-1 proteins
description	HIV type 1 (HIV-1) is characterized by its rapid genetic evolution, leading to challenges in anti-HIV therapy. However, the sequence variations in HIV-1 proteins are not randomly distributed due to a combination of functional constraints and genetic drift. In this study, we examined patterns of sequence variability for evidence of linked sequence changes (termed as coevolution or covariation) in 15 HIV-1 proteins. It shows that the percentage of charged residues in the coevolving residues is significantly higher than that in all the HIV-1 proteins. Most of the coevolving residues are spatially proximal in the protein structures and tend to form relatively compact and independent units in the tertiary structures, termed as “protein sectors”. These protein sectors are closely associated with anti-HIV drug resistance, T cell epitopes, and antibody binding sites. Finally, we explored candidate peptide inhibitors based on the protein sectors. Our results can establish an association between the coevolving residues and molecular functions of HIV-1 proteins, and then provide us with valuable knowledge of pathology of HIV-1 and therapeutics development.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324911/
_version_	1613186960611868672

Integrated Analysis of Residue Coevolution and Protein Structures Capture Key Protein Sectors in HIV-1 Proteins

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