Dr Joern Werner BBSRC HIV Inhibitor

In many cases the correct assembly of multiple proteins is critical for their biological function. By interfering specifically with certain protein-protein interactions one can control the assembly and as a result their function. The proteins that encapsulate the genetic information of the HIV virus undergo structural changes that change their arrangement from a spherical to a conical macromolecular assembly. The virus is only infections if the conical assembly is obtained. However, the protein-protein interactions that determine the spherical and the conical assemblies are not well understood. Several models for the arrangement have been proposed that are compatible with range of structural and biochemical data. We have a new small peptide that can interfere with both the spherical and conical assembly of the proteins in a yet unknown way. We are proposing to determine the interaction and the mechanism by which this peptide interferes with the formation of the assemblies. We intend to determine if the inhibitor simply blocks one or more important interfaces that are required for the assembly or whether it induces a conformational change or rearrangement in the protein such that assembly is disrupted. In addition we will determine the interaction of novel classes of molecules that have the same function. This will tell us if the mode of interaction of the inhibitor in hand is unique or if there are several solutions to the assembly inhibition. This will help us to understand the structural determinants that are required for the assembly and correct function of the HIV virus.