FIGURE 9.

Putative roles of interfacial hydrophobicity at gp41 preTM region. (A) Assembly of N-terminal amphipathic preTM region would hinder HR1-HR2 interactions. (a) Helical model for HIV-1 gp160 652QQEKNEQELLELDKWASLWNWFNIT676 sequence (underlined residues are part of the gp41 HR2 domain). Green side chains denote the residues participating in hydrophobic packing with HR1 helices in the gp41 six-helix bundle crystal structure. Red side chains belong to hydrophobic-at-interface residues of the N-terminal subdomain in the preTM. (b) Relative orientation of residues participating in hydrophobic packing with HR1 helices (green) and hydrophobic-at-interface residues (red) in prefusion (left) and postfusion structures (right). (B) Differential increase of monolayer surface by interfacial preTM may help fusion pore opening. A fractured TMC (a) might be brought to opened fusion pore (b) after hydrophobic-at-interface preTM (red) insertion into cis-monolayers. (C) Formation of fusion-competent gp41 complexes at the membrane surface. Fusion activation would lead to preTM insertion (a). Gp41 trimers (b, top view) would assemble into fusion-competent arrangements stabilized through preTM interactions (c, top view). Externally added HIV_c would interfere with the assembly of functional complexes in membranes (d, top view). PreTM, HR1, and HR2 are designated in red, purple, and green, respectively.