Disulfide exchange in CD4.
Explore the source record for details and available documents.
CD4 Antigens↗
Biomedical subjects
Lisa J Matthias
Publications and source records attributed to Lisa J Matthias.
Redox control on the cell surface: implications for HIV-1 entry.
Proteins that work outside cells nearly always contain disulfide bonds. The prevailing view is that these bonds have been added during evolution to enhance protein stability. Recent evidence suggests that disulfide bonds can also control protein function. Certain secreted proteins contain one or more disulfide bonds that can control function by breaking and reforming in a controlled way. This review focuses on disulfide exchange events on the cell surface, with a particular reference to two proteins involved in HIV-1 infection. The primary HIV-1 receptor on immune cells, CD4, and the viral envelope glycoprotein, gp120, play a central role in HIV-1 entry. Redox change in a disulfide bond or bonds in one or both of these proteins appears to be important for HIV-1 entry.
Anti-HIV Agents↗
Disulfide exchange in domain 2 of CD4 is required for entry of HIV-1.
CD4, a member of the immunoglobulin superfamily of receptors that mediates cell-cell interactions in the immune system, is the primary receptor for HIV-1. The extracellular portion of CD4 is a concatenation of four immunoglobulin-like domains, D1 to D4. The D1, D2 and D4 domains each contain a disulfide bond. We show here that the D2 disulfide bond is redox-active. The redox state of the thiols (disulfide versus dithiol) appeared to be regulated by thioredoxin, which is secreted by CD4(+) T cells. Locking the CD4 and the thioredoxin active-site dithiols in the reduced state with a hydrophilic trivalent arsenical blocked entry of HIV-1 into susceptible cells. These findings indicate that redox changes in CD4 D2 are important for HIV-1 entry and represent a new target for HIV-1 entry inhibitors.
Arsenicals↗