Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 428, Issue 13, Pages 2744-2757Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2016.05.003
Keywords
HIV-1; accessory gene products; Vpr; importin-alpha; induced-fit binding
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Funding
- RIKEN internal grants
- Health Sciences Research Grant from the Japanese Ministry of Health, Labor and Welfare (Research on HIV/AIDS) [11947234, 2637010]
- program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO) of Japan [7807510]
- Grants-in-Aid for Scientific Research [15K07068, 16K08824] Funding Source: KAKEN
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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 alpha-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-alpha, 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 beta-turn via an induced-fit mechanism, enabling binding to a minor nuclear localization signal (NLS) site of importin-alpha. The Vpr C-terminus can also bind with major NLS sites of importin-alpha 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. (C) 2016 Elsevier Ltd. All rights reserved.
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