||This article only describes one highly specialized aspect of its associated subject. (January 2014)|
Group-specific antigen (gag) is the genetic material that codes for the core structural proteins of a retrovirus.
It comprises part of the gag-inc fusion protein.
Gag in HIV
By convention, the HIV genome is numbered according to HIV subtype B reference strain HXB2.
Transcription and mRNA Processing
After a virus enters a target cell, the viral genome is integrated into the host cell chromatin. RNA polymerase II then transcribes the 9719 nucleotide full-length viral RNA. HIV Gag protein is encoded by the HIV gag gene, HXB2 nucleotides 790-2292.
HIV MA (p17) 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 myrisyl 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) myrisyl switch activation, the arachadonic 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 arachadonic acid moiety and the hydrophobic channel along the MA surface.
The CA is a 24 kDa protein fused to the C-terminus of MA in the unprocessed HIV Gag polyprotein. After viral maturation, 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.
SP1 (previously 'p2') is a 14-amino acid polypeptide intervening CA and NC. Cleavage of the CA-SP1 junction is the final step in viral maturation, which allows CA to condense into the viral capsid. SP1 is unstructured in solution but, in the presence of less polar solvents or at high polypeptide concentrations, it adopts an α-helical structure. In scientific research, western blots for CA (24 kDa) can indicate a maturation defect by the high relative presence of a 25 kDa band (uncleaved CA-SP1). SP1 plays a critical role in HIV particle assembly, although the exact nature of its role and the physiological relevance of SP1 structural dynamics are unknown.
HIV NC is a 7 kDa zinc finger protein in the Gag polyprotein and which, after viral maturation, forms the viral nucleocapsid. NC recruites full-length viral genomic RNA to nascent virions.
SP2 (previously 'p1') is a 16-amino acid polypeptide of unknown function which separates Gag polyprotein activities NC and p6.
HIV p6 is a 6 kDa polypeptide at the N-terminus of the Gag polyprotein. It recruits cellular proteins Tsg101 (a component of ESCRT-1) and Alix to initiate virus particle budding fromt the plasma membrane. p6 has no known function in the mature virus.
- Diagram at stanford.edu
- gag Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
- gag Genes at the US National Library of Medicine Medical Subject Headings (MeSH)
- gag Gene Products, Human Immunodeficiency Virus at the US National Library of Medicine Medical Subject Headings (MeSH)