Mutational analysis of HIV-2 Vpx shows that proline residue 109 in the poly-proline motif regulates degradation of SAMHD1

Halil Ibrahim Ciftci; Haruna Fujino; Ryoko Koga; Minami Yamamoto; Sogo Kawamura; Hiroshi Tateishi; Yasumasa Iwatani; Masami Otsuka; Mikako Fujita

doi:10.1016/j.febslet.2015.04.038

Mutational analysis of HIV-2 Vpx shows that proline residue 109 in the poly-proline motif regulates degradation of SAMHD1

FEBS Lett. 2015 Jun 4;589(13):1505-14. doi: 10.1016/j.febslet.2015.04.038. Epub 2015 Apr 30.

Authors

Halil Ibrahim Ciftci¹, Haruna Fujino¹, Ryoko Koga¹, Minami Yamamoto¹, Sogo Kawamura¹, Hiroshi Tateishi¹, Yasumasa Iwatani², Masami Otsuka¹, Mikako Fujita³

Affiliations

¹ Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
² Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Nagoya, Japan.
³ Research Institute for Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto, Japan. Electronic address: mfujita@kumamoto-u.ac.jp.

PMID: 25936766
DOI: 10.1016/j.febslet.2015.04.038

Abstract

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.

Keywords: HIV-2; Poly-proline; SAMHD1; Vpx.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Motifs / genetics
Amino Acid Sequence
Base Sequence
Cell Line, Tumor
HEK293 Cells
HIV-2 / genetics
HIV-2 / metabolism*
Humans
Immunoblotting
Molecular Sequence Data
Monomeric GTP-Binding Proteins / genetics
Monomeric GTP-Binding Proteins / metabolism*
Mutant Proteins / genetics
Mutant Proteins / metabolism
Mutation
Proline / genetics
Proline / metabolism*
Proteolysis
SAM Domain and HD Domain-Containing Protein 1
Viral Regulatory and Accessory Proteins / genetics
Viral Regulatory and Accessory Proteins / metabolism*

Substances

Mutant Proteins
VPX protein, Human immunodeficiency virus 2
Viral Regulatory and Accessory Proteins
Proline
SAM Domain and HD Domain-Containing Protein 1
SAMHD1 protein, human
Monomeric GTP-Binding Proteins