Structural studies of Vpx, the accessory protein of the HIV-2
We are looking for a candidate to apply for a 2 years postdoctoral position in
the Laboratory of Biological NMR and Crystallography at the University Paris
Descartes. The project will aim to determine the structure of the Vpx protein
(112 amino acids) and of its complexes with inhibitors identified after
screening of small compound libraries, using high-field multidimensional NMR
and Molecular Modeling. HIV-2 is the second leading cause of AIDS in humans and
we are interested with the Vpx protein that increases the efficiency of
infection by lentivectors of various origins, allows the transport of viral DNA
to the nucleus and promotes the accumulation of retroviral DNA in some cells of
the immune system. Vpx thus allows viral dissemination but its role in the
replication of HIV-2 and its molecular mechanism are still not understood.
The objectives of this project are to understand at the structural and
mechanistic level, how Vpx inhibits cell defenses against viral infection. We
aim to identify partners of Vpx in cells and to elucidate its exact role in
viral dissemination and its role in the replication of HIV-2. Finally, we want
to understand how cellular factors can modulate the early stages of lentiviral
infection. The obtaining the Vpx protein structure, identification of partners
and the study of their complexes will make our contribution to the
understanding of the mechanisms involved in the various activities of this
protein. The study of the protein Vpx will be greatly simplified by the
experience we have gained from structural and functional studies performed on
the Vpr protein.
The protein Vpx has been obtained by chemical synthesis and will be produced by
overexpression in Coli and 15N labeled. The project will be based on functional
and structural experiments that associate liquid-state Nuclear Magnetic
Resonance and Molecular Modeling. The candidate should have a good experience
in the protein overexpression et their purification in bacterial systems and a
good expertise in multidimensional heteronuclear NMR and molecular modeling.
The starting date is January 2012 for a two years funding. Application, CV and
reference letters should be submitted to:
Dr Serge Bouaziz
serge.bouaziz@parisdescartes.fr
http://lcrbw.pharmacie.univ-paris5.fr/
