Mutations that mimic phosphorylation of the HIV-1 matrix protein do not perturb the myristyl switch.

Recent studies indicate that the matrix domain (MA) of the HIV-1 Gag polyprotein directs Gag to the plasma membrane for virus assembly via a phosphatidylinositol-4,5-bisphosphate (PIP(2))-dependent myristyl switch mechanism. MA also has been reported to direct nuclear trafficking via nuclear import and export functions, and some studies suggest that nuclear targeting may be regulated by MA phosphorylation (although this proposal remains controversial). We have prepared and studied a series of HIV-1 MA mutants containing Ser-to-Asp substitutions designed to mimic phosphorylation, including substitutions in regions of the protein involved in protein-protein interactions and known to influence the myristyl switch (S6D, S9D, S67D, S72D, S6D/S9D, and S67D/S72D).

Electrostatic interactions drive membrane association of the human immunodeficiency virus type 1 Gag MA domain.

The assembly of most retroviruses occurs at the plasma membrane. Membrane association is directed by MA, the N-terminal domain of the Gag structural protein. For human immunodeficiency virus type 1 (HIV-1), this association is mediated in part by a myristate fatty acid modification.

Biochemical characterization of rous sarcoma virus MA protein interaction with membranes.

The MA domain of retroviral Gag proteins mediates association with the host cell membrane during assembly. The biochemical nature of this interaction is not well understood. We have used an in vitro flotation assay to directly measure Rous sarcoma virus (RSV) MA-membrane interaction in the absence of host cell factors.