Mutational analysis of HIV-2 Vpx shows that proline residue 109 in the poly-proline motif regulates degradation of SAMHD1.
In this study, we performed a mutational analysis to determine whether the mechanism by which HIV-2 Vpx confers the capacity for infectivity and viral replication in macrophages is solely dependent on its ability to degrade the host antiviral factor SAMHD1. Contrary to expectations, we demonstrated that P(109) in the C-terminal poly-proline motif of HIV-2 Vpx has two unique roles: to facilitate the specific degradation of SAMHD1 in macrophages, and to facilitate multimerization of Vpx, therefore preventing SAMHD1 degradation in the presence of high levels of Vpx.
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Halil Ibrahim
HI
Ciftci
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Haruna
H
Fujino
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Ryoko
R
Koga
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Minami
M
Yamamoto
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Sogo
S
Kawamura
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Hiroshi
H
Tateishi
Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
Yasumasa
Y
Iwatani
Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Masami
M
Otsuka
Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto, Japan. Electronic address: mfujita@kumamoto-u.ac.jp.
Mikako
M
Fujita
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011392:Proline / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D000076106:SAM Domain and HD Domain-Containing Protein 1; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*
D050505:Mutant Proteins; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D011392:Proline; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
HIV-2; Poly-proline; SAMHD1; Vpx