Research Overview
MECHANISMS OF VIRAL MEMBRANE FUSION
We are using a combination of biophysical, structural, and biochemical approaches to study the three-dimensional structure and biological function of the HIV-1 envelope glycoprotein that mediates fusion of viral and cellular membranes. We hope to establish the biophysical and structural basis of the conformational changes in the gp120/gp41 complex that are required for activation of membrane fusion. Our long-term goal is to gain a detailed understanding of the structural, biophysical and biological properties of the HIV-1 glycoprotein complex, and to relate this understanding to its in vivo function. This includes defining both the native and fusogenic conformations of gp41, the nature of its conformational change, and the role of gp120 in controlling this structural rearrangement, and characterizing the functional determinants in both the gp41 core and peptides found to have antiviral activity. We make use of structural dissection of proteins into modules. This methodology can make it possible to develop and study simple model systems that display the essential features to be examined. Determining structural details of these modules at atomic resolution further allows us to attack fundamental mechanistic questions in biology in greater details than is often possible by starting with larger, more complex systems.
