HIV-1 matrix organizes as a hexamer of trimers on membranes containing phosphatidylinositol-(4,5)-bisphosphate.
The human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein represents the N-terminal domain of the HIV-1 precursor Gag (PrGag) protein and carries an N-terminal myristate (Myr) group. HIV-1 MA fosters PrGag membrane binding, as well as assembly of envelope (Env) proteins into virus particles, and recent studies have shown that HIV-1 MA preferentially directs virus assembly at plasma membrane sites enriched in cholesterol and phosphatidylinositol-(4,5)-bisphosphate (PI[4,5]P(2)). To characterize the membrane binding of MA and PrGag proteins, we have examined how Myr-MA proteins, and proteins composed of Myr-MA and its neighbor Gag capsid (CA) protein associate on membranes containing cholesterol and PI[4,5]P(2). Our results indicate that Myr-MA assembles as a hexamer of trimers on such membranes, and imply that MA trimers interconnect CA hexamer rings in immature virus particles. Our observations suggest a model for the organization of PrGag proteins, and for MA-Env protein interactions.