title: Integrated analysis of residue coevolution and protein structures capture key protein sectors in HIV-1 proteins.
abstract: 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.
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, No.32 Jiaochang Donglu Kunming, 650223 Yunnan, China; Department of Integrative Biology and Physiology, University of California, Los Angeles, 610 Charles E. Young Drive East, Los Angeles, California, United States of America.
authors: Yuqi
authors: Y
authors: Zhao
authors: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors: Yanjie
authors: Y
authors: Wang
authors: Kunming Biological Diversity Regional Center of Instruments, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors: Yuedong
authors: Y
authors: Gao
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, No.32 Jiaochang Donglu Kunming, 650223 Yunnan, China.
authors: Gonghua
authors: G
authors: Li
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, No.32 Jiaochang Donglu Kunming, 650223 Yunnan, China; Collaborative Innovation Center for Natural Products and Biological Drugs of Yunnan, Kunming, Yunnan 650223, China.
authors: Jingfei
authors: J
authors: Huang
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D019295:Computational Biology; D024882:Drug Resistance, Viral / Q000235:genetics; D000939:Epitopes / Q000378:metabolism; D019143:Evolution, Molecular; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D000939:Epitopes; D054298:Human Immunodeficiency Virus Proteins