test_moissonnage_selune
type: Agent

The crystallographic study of the catalytic core domain of the avian rous associated virus type 1 (rav-1) integrase reveals a novel dimeric assembly
type: Distribution
access URL: https://theses.hal.science/tel-00865880
format: HTML
issued: 2026-05-09T14:56:52.311423
modified: 2026-05-09T14:56:52.290710

The crystallographic study of the catalytic core domain of the avian rous associated virus type 1 (rav-1) integrase reveals a novel dimeric assembly
type: Dataset
contact point: Organization
  fn: CCSD
keyword: interface-dimerique
keyword: cristallographie
keyword: integrase
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: dimeric-interface
keyword: avian-leukemia-virus
keyword: relation-structure-fonction
keyword: theses
keyword: infoeu-reposemanticsdoctoralthesis
keyword: catalytic-core-domain
keyword: structure-function-link
keyword: crystallography
landing page: https://theses.hal.science/tel-00865880
description: During the replicative cycle of retroviruses, the retrotranscribed viral DNA is integrated into the host chromosome by the viral integrase protein (IN). The integration reaction is essential for the viral life cycle. Therefore, IN is a key target for antiretroviral drug design to treat HIV infection. IN consists of three domains (N-terminal, central and Cterminal) connected by flexible loops, making the enzyme difficult to crystallize. Dr C. Ronfort (Team Retrovirus and Retroviral Integration) and Pr P. Gouet (BioCrystallography Laboratory) collaborate since 2002 in Lyon to study IN from the Rous Associated Virus type 1 (RAV-1). My thesis work lies within this collaboration. Its objective was to perform crystallographic and molecular studies of the central domain of RAV-1 IN and of mutants of interest identified by the team of Dr C. Ronfort. In this aim, the IN fragment has been overexpressed and purified. Its crystal structure has been solved to a resolution of 1.8 Å. The observation of this structure reveals that the RAV-1 IN can exhibit a novel dimeric arrangement with a molecular interface stabilized by three pairs of facing α-helices. This arrangement is also characterized by the presence of a basic narrow groove at its surface. Thanks to biochemical in vitro experiments and in silico docking studies, we have shown that this median groove could allow the binding of a linear singlestranded RNA. Moreover, our experimental data can explain how the crystallization conditions as well as the mutation of a specific residue located at the surface of the enzyme favor either this novel dimeric arrangement or the classical dimeric interface. Therefore, the data obtained during this thesis suggest that IN exhibits modular structural properties, allowing it to operate in several distinct steps of the retroviral cycle in presence of dsDNA (integration) or ssRNA (reverse transcription and/or encapsidation of the retroviral RNA genome)
identifier: NNT: 2010LYO10251
issued: 2026-05-09T14:56:52.304967
language: fr
modified: 2026-05-09T14:56:52.304971