FIGURE 2.

(A–D) Close-up views of structures of HIV-1, HIV-2, and M-PMV MA proteins bound to lipids. MA proteins are shown in ribbon and surface representations with residues implicated in binding shown as sticks. Phospholipids are shown as green [PI(4,5)P₂] or blue (PC) sticks and their acyl chains involved in binding are shown in cyan. (A) HIV-1 myr(–)MA bound to di-C₈-PI(4,5)P₂ (PDB ID: 2H3V). (B) HIV-1 myr(–)MA bound to di-C₈-PC (PDB ID: 2LYA). (C) HIV-2 MA bound di-C₄-PI(4,5)P₂ (PDB ID: 2K4I). (D) M-PMV MA bound to di-C₈-PI(4,5)P₂ structure provided by Prchal et al. (2012). (E) Cryoelectron microscopy reconstruction of HIV-1 immature particle in a section with (left) or without (right) Gag polyprotein present. Used with permission [Copyright (2009) National Academy of Sciences, USA (Briggs et al., 2009)]. (F) A schematic representation of potential mechanisms for Gag binding to the PM for different retroviruses. Gag binding to membranes is regulated by PI(4,5)P₂ and RNA for some but not all retroviruses. Binding of Gag to membranes via the MA domain displaces RNA, which binds non-specifically to the basic region of MA. Data are not in agreement on the role of PI(4,5)P₂ in MLV Gag binding to the PM. For EIAV, Gag binding to membranes appears to have no specific requirement for PI(4,5)P₂ since other phosphoinositides may also play a role. For M-PMV, Gag assembly occurs in the cytoplasm prior to transport to the PM where MA specifically recognizes PI(4,5)P₂.