Characterization and molecular basis of the oligomeric structure of HIV- 1 Nef protein

Stefan Arold, François Hoh, Stephanie Domergue, Catherine Birck, Marc André Delsuc, Magali Jullien, Christian Dumas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The Nef protein of human immunodeficiency virus type I (HIV-1) is an important determinant for the onset of AIDS disease. The self-association properties of HIV-1 Nef are analyzed by chemical cross-linking, dynamic light scattering, equilibrium analytical ultracentrifugation, and NMR spectroscopy. The experimental data show that the HIV-1 Nef core domain forms stable homo- dimers and trimers in solution, but not higher oligomers. These Nef homomers are not covalently linked by disulfide bridges, and the equilibrium between these forms is dependent on the Nef concentration. We further provide the molecular basis for the Nef core dimers and trimers obtained by analysis of crystallographic models. Oligomerization of biological polypeptides is a common tool used to trigger events in cellular signaling and endocytosis, both of which are targeted by Nef. The quaternary structure of Nef may be of physiological importance and may help to connect its cellular targets or to increase affinity of the viral molecule for its ligands. The herein described models for Nef dimers and trimers will allow further mutational studies to elucidate their role in vivo. These results provide novel insight into the structural and functional relationships of this important viral protein. Moreover, the oligomer interface may represent a novel target for the design of antiviral agents.

Original languageEnglish (US)
Pages (from-to)1137-1148
Number of pages12
JournalProtein Science
Volume9
Issue number6
DOIs
StatePublished - Jan 1 2000

Keywords

  • Chemical cross-linking
  • Dynamic light scattering
  • HIV- 1
  • NMR
  • Nef
  • Oligomerization
  • Sedimentation equilibrium

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Characterization and molecular basis of the oligomeric structure of HIV- 1 Nef protein'. Together they form a unique fingerprint.

Cite this