Membrane-induced conformational change during the activation of HIV-1 gp41

The human immunodeficiency virus type 1 gp41 ectodomain forms a three-hairp in protease-resistant core in the absence of membranes, namely, the putativ e gp41 fusion-active state. Here, we show that recombinant proteins corresp onding to the ectodomain of gp41, but lacking the fusion peptide, bind memb ranes and consequently undergo a major conformational change. As a result, the protease-resistant core becomes susceptible to proteolytic digestion. A ccordingly, synthetic peptides corresponding to the segments that construct this core bind the membrane. It is remarkable that the hetero-oligomer for med by these peptides dissociates upon binding to the membrane. These resul ts are consistent with a model in which, after the three-hairpin conformati on is formed, membrane binding induces opening of the gp41 core complex. We speculate that binding of the segments that constructed the core to the vi ral and cellular membranes could bring the membranes closer together and fa cilitate their merging. (C) 2000 Academic Press.