From receptor recognition mechanisms to bioinspired mimetic antagonists inHIV-1/cell docking

Understanding the ways in which two or more proteins interact may give insi ght into underlying binding and activation mechanisms in biology, methods f or protein separation and structure-based antagonism. This review describes ways in which protein recognition has been explored in our laboratory for the HIV-1/cell entry process, initial contact between an HIV-1 virion parti cle and a human cell occurs between gp120 (an HIV-1 envelope protein) and C D4 (a human extracellular signaling protein), This interaction leads to a s equence of events which includes a conformational change in gp120, fusion o f the HIV-1 and cellular membranes and eventual infection of the cell, Usin g an optical biosensor and a reporter antibody, we have been able to measur e the conformational change in gp120 that occurs upon CD4 binding. We also have used this biosensor system to characterize CD4 mimetics, obtained by p eptide synthesis in miniprotein scaffolds. Phage display techniques have be en employed to identify novel miniprotein sequences. The combination of bio sensor interaction kinetics analysis and phage display provides a useful ap proach for understanding the recognition mechanisms involved in the HIV/cel l docking process. This approach may also be useful in investigating other protein complexes of importance in health and disease. (C) 2001 Elsevier Sc ience B.V. All rights reserved.