Mission

The HARC Center is focused upon determining structures of five HIV proteins (Integrase, Tat, Rev, Vif and Nef) and their complexes with a diverse array of cellular partners, including host proteins and RNA or DNA. These proteins and their complexes perform essential regulatory and acccessory functions during the viral lifecycle.

Viral-host cell complexes range from binary protein-protein or protein-nucleic acid complexes to much larger multicomponent assemblies. The Center seeks to structurally characterize these assemblies in a comprehensive manner, starting with validation of known protein partners, and identification of new partners, using the powerful technique of tandem affinity purification and mass spectrometry, derived from yeast proteomic studies. Based on these and other results, known complexes are expressed, purified and structurally characterized in various states of assembly using NMR, crystallography and cryo-EM.

These structures can then be combined with computational techniques (e.g. docking of known inhibitor libraries) to better understand how viral proteins recognize their host cell partners, and how these interactions can be disrupted for the purpose of preventing or attenuating viral proliferation, and thereby the progression of the AIDS disease.