RECEPTOR-INDUCED CONFORMATIONAL-CHANGES IN THE SUBGROUP-A AVIAN-LEUKOSIS AND SARCOMA-VIRUS ENVELOPE GLYCOPROTEIN

We recently reported that Tva, the host cell receptor for subgroup A a vian leukosis and sarcoma viruses, binds specifically to the subgroup A envelope glycoprotein (Env-A) (J. M Gilbert, P. Bates, H. E. Varmus, and J. M. White, J. Virol. 68:5623-5628, 1994). Here we have tested t he hypothesis that binding of Tva causes conformational changes in Env -A that correlate with its conversion from a fusion-inactive to a fusi on-active state. Conformational changes were examined by both a proteo lysis and an immunoprecipitation assay. A temperature-dependent confor mational change, demonstrated by the generation of a specific thermoly sin digestion product of the surface (SU) subunit, occurred when a sol uble form of Tva (sTva) was incubated with Env-A. sTva did not induce this conformational change in Env-C or in a noninfectious precursor fo rm of Env-A, Env-A CL. However sTva did induce the conformational chan ge in Env-A CL that had been pretreated in vitro to produce the SU and transmembrane (TM) subunits, Moreover, interaction of Tva with Env-A at 25 degrees C, but not at 4 degrees C, appeared to reveal a previous ly buried segment of the putative fusion peptide of Env-A Our results suggest that binding of Tva to Env-A results in specific conformationa l changes in the Env-A glycoprotein that are relevant to the activatio n of its fusion function.