title: The 57th amino acid conveys the differential subcellular localization of human immunodeficiency virus-1 Tat derived from subtype B and C.
abstract: The multifunctional transactivator Tat protein is an essentially regulatory protein for HIV-1 replication and it plays a role in pathogenesis of HIV-1 infection. At present, numerous experimental studies about HIV-1 Tat focus on subtype B, very few has been under study of subtype C-Tat. In view of the amino acid variation of the clade-specific Tat proteins, we hypothesized that the amino acid difference contributed to differential function of Tat proteins. In the present study, we documented that subtype B NL4-3 Tat and subtype C isolate HIV1084i Tat from pediatric patient in Zambia exhibited distinct nuclear localization by over-expressing fusion protein Tat-EGFP. Interestingly, 1084i Tat showed uniform nuclear distribution, whereas NL4-3 Tat primarily localized in nucleolus. The 57th amino acid, highly conserved between B-Tat (arginine) and C-Tat (serine), is located in the basic domain of Tat, and played an important role in this subcellular localization. Meanwhile, we found that substitution of arginine to serine at the site 57 decreases Tat transactivation of the HIV-1 LTR promoter.
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Qian
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Di
authors.initials: D
authors.lastname: Qi
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shen
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Medical Molecular Virology, School of Medicine, Nankai University, Weijin Road No. 94, Nankai District, Tianjin, 300071, China. kongxh@nankai.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Kong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D005838:Genotype; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space; D009154:Mutation; D019913:Nuclear Localization Signals; D009690:Nucleic Acid Conformation; D056510:Position-Specific Scoring Matrices; D021381:Protein Transport; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: 57th arginine/serine; Nucleolus localization; SUBTYPE B/C; Tat; Transactivity
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