title: Molecular Mechanism of HIV-1 Vpr for Binding to Importin-α.
abstract: Viral protein R (Vpr) is an accessory gene product of human immunodeficiency virus type 1 (HIV-1) that plays multiple important roles associated with viral replication. Structural studies using NMR have revealed that Vpr consists of three α-helices and contains flexible N- and C-termini. However, the molecular mechanisms associated with Vpr function have not been elucidated. To investigate Vpr multifunctionality, we performed an X-ray crystallographic study of Vpr complexes containing importin-α, a known Vpr binding partner present in host cells. Elucidation of the crystal structure revealed that the flexible C-terminus changes its conformation to a twisted β-turn via an induced-fit mechanism, enabling binding to a minor nuclear localization signal (NLS) site of importin-α. The Vpr C-terminus can also bind with major NLS sites of importin-α in an extended conformation in different ways. These results, which represent the first reported crystallographic analysis of Vpr, demonstrate the multifunctional aspects that enable Vpr interaction with a variety of cellular proteins.
authors.affiliation: Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address: miyatake@riken.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Miyatake
authors.affiliation: Protein Wave Corporation, 1-16-5 Nishitomigaoka, Nara 631-0006, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sanjoh
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Matsuda
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Sato
authors.affiliation: Laboratory of Nuclear Transport Dynamics, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki-shi, Osaka, 567-0085, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Center for Sustainable Resource Science, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address: aida@riken.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aida
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019913:Nuclear Localization Signals / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology; D028901:alpha Karyopherins / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D016336:Gene Products, vpr; D019913:Nuclear Localization Signals; D028901:alpha Karyopherins; D054325:vpr Gene Products, Human Immunodeficiency Virus
keywords: HIV-1; Vpr; accessory gene products; importin-α; induced-fit binding