Group-specific antigen

Group-specific antigen, or gag, is the polyprotein that contains the core structural proteins of an Ortervirus (except Caulimoviridae).

All orthoretroviral gag proteins are processed by the protease (PR or pro) into MA (matrix), CA (capsid), NC (nucleocapsid) parts, and sometimes more.

It is responsible for targeting Gag polyprotein to the plasma membrane via interaction with PI(4,5)P2 through its highly basic region (HBR).

[3] In parallel to (or possibly concomitant with) myristoyl switch activation, the arachidonic acid moiety of PI(4,5)P2 is extracted from the plasma membrane and binds in a channel on the surface of MA (which is distinct from that previously occupied by the MA myristoyl group.

While MA, IN, VPR, and cPPT had been previously implicated as factors in HIV's ability to target non-dividing cells, CA has been shown to be the dominant determinant of retrovirus infectivity in non-dividing cells, which is key in helping to avoid insertional mutagenesis in lentiviral gene therapy.

SP1 is unstructured in solution but, in the presence of less polar solvents or at high polypeptide concentrations, it adopts an α-helical structure.

[citation needed] Spacer peptide 2 (SP2, previously 'p1') is a 16-amino acid polypeptide of unknown function which separates Gag proteins NC and p6.

[6] It recruits cellular proteins TSG101 (a component of ESCRT-I) and ALIX to initiate virus particle budding from the plasma membrane.

[11] The animal Activity-regulated cytoskeleton-associated protein (ARC) gene is repurposed from the metaviral gag.

[13] Caulimoviridae members rarely get a gag assignment to its capsid-containing ORF, but the CP-PRO-POL layout does show analogy with the canonical gag-pol setup.