title: From receptor recognition mechanisms to bioinspired mimetic antagonists in HIV-1/cell docking.
abstract: Understanding the ways in which two or more proteins interact may give insight into underlying binding and activation mechanisms in biology, methods for 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 particle and a human cell occurs between gp120 (an HIV-1 envelope protein) and CD4 (a human extracellular signaling protein). This interaction leads to a sequence of events which includes a conformational change in gp120, fusion of the HIV-1 and cellular membranes and eventual infection of the cell. Using an optical biosensor and a reporter antibody, we have been able to measure the conformational change in gp120 that occurs upon CD4 binding. We also have used this biosensor system to characterize CD4 mimetics, obtained by peptide synthesis in miniprotein scaffolds. Phage display techniques have been employed to identify novel miniprotein sequences. The combination of biosensor interaction kinetics analysis and phage display provides a useful approach for understanding the recognition mechanisms involved in the HIV/cell docking process. This approach may also be useful in investigating other protein complexes of importance in health and disease.
authors.affiliation: Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104-6100, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Dowd
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: I M
authors.initials: IM
authors.lastname: Chaiken
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D018716:Molecular Mimicry
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120