The HIV‐1 Vpr co‐activator induces a conformational change in TFIIB

FEBS Letters

Bouhamdan, Mohamad²  Pomerantz, Roger²  Rey, Françoise¹  Agostini, Isabelle¹  Sire, Joséphine¹  Vigne, Robert¹  Spire, Bruno¹  Willetts, Karen¹  Navarro, Jean-Marc¹ 

[1] INSERM U372, 163 avenue de Luminy, BP 178, 13276 Marseille Cedex 09, France;The Dorrance H. Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, 1020 Locust St., Room 329, Philadelphia, PA 19107, USA

关键词: HIV-1 Vpr;    TFIIB;    Transactivation;    Conformation change;   

DOI  :  10.1016/S0014-5793(99)00501-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Vpr is a HIV-1 virion-associated protein which plays a role in viral replication and in transcription and cell proliferation. We have previously reported that Vpr stimulates transcription of genes lacking a common DNA target sequence likely through its ability to interact with TFIIB. However, the molecular mechanism of the Vpr-mediated transcription remains to be precisely defined. In this in vitro study, we show that the binding site of Vpr in TFIIB overlaps the domain of TFIIB which is engaged in the intramolecular bridge between the N- and C-terminus of TFIIB, highly suggesting that binding of Vpr may induce a change in the conformation of TFIIB. Indeed, with a partial proteolysis assay using V8 protease, we demonstrate that Vpr has the ability to change the conformation of TFIIB. We investigated in this partial proteolysis assay a series of Vpr-mutated proteins previously defined for their transactivation properties. Our data show a correlation between the ability of Vpr-mutated proteins to stimulate transcription and their ability to induce a conformational change in TFIIB, indicating a functional relevance of the Vpr-TFIIB interaction.

【 授权许可】

Unknown