The structure of furin-cleaved DENV at pH 6.0 shows that pr is bound to the virion through interactions with the DII tip of one E protein and DI on the neighboring E monomer [35, 36] . This suggested that pr might primarily block virus-membrane interaction by preventing dissociation of E dimers, a required first step in the fusion pathway [55] . Our results show efficient binding of pr to the dimeric form of the DENV E protein, but also to the monomeric DI/II form. We do not know if the E9 protein dimer is stabilized by pr interaction or if the dimer dissociates prior to interaction with pr, and experiments to address these points were inconclusive (data not shown). The similar pH dependence of pr binding to monomeric and dimeric E proteins suggests that pr may bind the same site in both cases. mAb 4G2 against the fusion loop inhibited pr interaction with E DI/II, confirming that pr was binding to the DII tip rather than to other sites on expressed E proteins. In keeping with its binding site in the vicinity of the fusion loop, pr peptide blocked the membrane insertion and liposome co-floatation of E9 and DI/II proteins. Prior studies showed that a monomeric DI/II protein with a single Strep affinity tag stably inserts into liposomes at either neutral or low pH [30] , and pr blocked this insertion even at pH 8.0 where its interaction with DI/II was suboptimal (data not shown). Thus, while the pr-E interaction is strongly low pH-dependent, its functional inhibition of membrane insertion can still be observed at neutral pH in the presence of excess pr.