Group-specific antigen

Group-specific antigen, or gag, is the genetic material that codes for the core structural proteins of a retrovirus. Group-specific antigen, or gag, is the genetic material that codes for the core structural proteins of a retrovirus. It comprises part of the gag-onc fusion protein. By convention, the HIV genome is numbered according to HIV subtype B reference strain HXB2. After a virus enters a target cell, the viral genome is integrated into the host cell chromatin. RNA polymerase II then transcribes the 9181 nucleotide full-length viral RNA. HIV Gag protein is encoded by the HIV gag gene, HXB2 nucleotides 790-2292. The HIV p17 matrix protein (MA) is a 17 kDa protein, of 132 amino acids, which comprises the N-terminus of the Gag polyprotein. It is responsible for targeting Gag polyprotein to the plasma membrane via interaction with PI(4,5)P2 through its highly basic region (HBR). HIV MA also makes contacts with the HIV trans-membrane glycoprotein gp41 in the assembled virus and, indeed, may have a critical role in recruiting Env glycoproteins to viral budding sites. Once Gag is translated on ribosomes, Gag polyproteins are myristoylated at their N-terminal glycine residues by N-myristoyltransferase 1. This is a critical modification for plasma membrane targeting. In the membrane-unbound form, the MA myristoyl fatty acid tail is sequestered in a hydrophobic pocket in the core of the MA protein. Recognition of plasma membrane PI(4,5)P2 by the MA HBR activates the 'myristoyl switch', wherein the myristoyl group is extruded from its hydrophobic pocket in MA and embedded in the plasma membrane. 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. HIV Gag is then tightly bound to the membrane surface via three interactions: 1) that between the MA HBR and the PI(4,5)P2 inositol phosphate, 2) that between the extruded myristoyl tail of MA and the hydrophobic interior of the plasma membrane, and 3) that between the PI(4,5)P2 arachidonic acid moiety and the hydrophobic channel along the MA surface. The p24 capsid protein (CA) is a 24 kDa protein fused to the C-terminus of MA in the unprocessed HIV Gag polyprotein. After viral maturation, CA forms the viral capsid. CA has two generally recognized domains, the C-terminal domain (CTD) and the N-terminal domain (NTD). The CA CTD and NTD have distinct roles during HIV budding and capsid structure. When a Western blot test is used to detect HIV infection, p24 is one of the three major proteins tested for, along with gp120/gp160 and gp41.