HIV-1 Gag capsid-spacer peptide 1 junction six-helix bundle (CA-SP1 6HB) (CA-SP1 6HB)

The HIV-1 Gag CA-SP1 junction six-helix bundle is a critical structural intermediate formed during the assembly and maturation of the human immunodeficiency virus type 1 (HIV-1). This bundle is composed of the C-terminal region of the capsid (CA) protein and the adjacent spacer peptide 1 (SP1) within the Gag polyprotein precursor (PubMed: 27143420). During viral maturation, the HIV-1 protease must cleave the Gag polyprotein at several sites, with the CA-SP1 junction being the final and rate-limiting step (PubMed: 28652401). The formation of the six-helix bundle is essential for the assembly of the immature hexagonal lattice, but it must be disassembled via proteolysis to allow for the formation of the mature, infectious conical core (PubMed: 30045870). This structure is the specific pharmacological target of maturation inhibitors (MIs), such as bevirimat and GSK3640254 (PubMed: 34153344). MIs bind within the central pore of the bundle, stabilizing it and preventing the protease from accessing the cleavage site (PubMed: 27143420). This inhibition results in the release of defective, immature virus particles that are unable to infect new cells, providing a unique mechanism of action distinct from other antiretroviral classes (PubMed: 32814564).

Other names

CA-SP1 junctionGag CA-SP1 cleavage siteHIV-1 maturation inhibitor binding siteCA-SP1 six-helix bundle

Maturation inhibition via stabilization of the CA-SP1 six-helix bundle, which sterically hinders HIV-1 protease from cleaving the junction, leading to the production of non-infectious, immature virions.