Formation of transient dimers by a retroviral protease

The Biochemical Journal
Maximilian J HartlBirgitta M Wöhrl

Abstract

Retroviral proteases have been shown previously to be only active as homodimers. They are essential to form the separate and active proteins from the viral precursors. Spumaretroviruses produce separate precursors for Gag and Pol, rather than a Gag and a Gag-Pol precursor. Nevertheless, processing of Pol into a PR (protease)-RT (reverse transcriptase) and integrase is essential in order to obtain infectious viral particles. We showed recently that the PR-RT from a simian foamy virus, as well as the separate PRshort (protease) domain, exhibit proteolytic activities, although only monomeric forms could be detected. In the present study, we demonstrate that PRshort and PR-RT can be inhibited by the putative dimerization inhibitor cholic acid. Various other inhibitors, including darunavir and tipranavir, known to prevent HIV-1 PR dimerization in cells, had no effect on foamy virus protease in vitro. 1H-15N HSQC (heteronuclear single quantum coherence) NMR analysis of PRshort indicates that cholic acid binds in the proposed PRshort dimerization interface and appears to impair formation of the correct dimer. NMR analysis by paramagnetic relaxation enhancement resulted in elevated transverse relaxation rates of those amino acids predi...Continue Reading

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Citations

May 7, 2010·Medical Microbiology and Immunology·Axel Rethwilm
Jan 3, 2012·Journal of Biomolecular Structure & Dynamics·Maximilian J HartlStephan Schwarzinger
Feb 18, 2011·Journal of Virology·Maximilian J HartlBirgitta M Wöhrl
Oct 14, 2011·Viruses·Dirk Lindemann, Axel Rethwilm
Mar 23, 2013·Viruses·Eun-Gyung LeeMaxine L Linial
Nov 5, 2010·Journal of Biomolecular NMR·Alexander N VolkovNico A J van Nuland
Oct 15, 2013·Current Opinion in Virology·Axel Rethwilm
Sep 3, 2016·Viruses·Martin V Hamann, Dirk Lindemann
Jun 25, 2015·Microbiology Spectrum·Anna Marie Skala
Jul 8, 2021·Journal of Virology·Marzena NowackaMarcin Nowotny
May 8, 2012·Journal of Chemical Theory and Computation·Danzhi Huang, Amedeo Caflisch

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