BiP-binding sequences in HIV gp160 - Implications for the binding specificity of BiP

BiP, a resident endoplasmic reticulum member of the HSP70 family of molecul ar chaperones, associates transiently with a wide variety of newly synthesi zed exocytotic proteins. In addition to immunoglobulin heavy and light chai ns, the first natural substrates identified for BiP, a number of viral poly peptides including the human immunodeficiency virus type 1 envelope glycopr otein gp160 interact with BiP during their passage through the endoplasmic reticulum. We have used a computer algorithm developed to predict BiP-bindi ng sites within protein primary sequences to identify sites within gp160 th at might mediate its association with BiP. Analysis of the ability of 22 sy nthetic heptapeptides corresponding to predicted binding sites to stimulate the ATPase activity of BiP or to compete with an unfolded polypeptide for binding to BiP indicated that about half of them are indeed recognized by t he chaperone. All of the confirmed binding sites are localized within conse rved regions of gp160, suggesting a conserved role for BiP in the folding o f gp160. Information on the characteristics of confirmed BiP-binding peptid es gained in this and previous studies has been utilized to improve the pre dictive power of the BiP Score algorithm and to investigate the differences in peptide binding specificities of HSP70 family members.