Snapshot of the interaction between HIV envelope glycoprotein 120 and protein disulfide isomerase.

The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein 120 (gp120) binds to cell surface receptors and mediates HIV entry. Previous studies suggest the cell surface protein disulfide isomerase (PDI) might interact with disulfide bond(s) of gp120 and thus facilitate HIV-1 entry. In the present study, a kinetic trapping approach was used to capture the disulfide cross-linking intermediate between gp120 and PDI. Active site mutant PDIs were prepared in which the C-terminal cysteine at the active site was replaced by a serine. The active site mutant PDIs were able to covalently cross-link with gp120 through a mixed disulfide bond in vitro. The cross-linking efficiency was enhanced by CD4 protein (primary receptor of HIV-1) and was inhibited both by bacitracin (a PDI inhibitor) and by catalytically inactive PDI. The present results suggested the cell surface PDI might play a role in HIV entry in vivo.