HIV-1 Gag capsid-spacer peptide 1 (CA-SP1) cleavage site (CA-SP1 junction)

The CA-SP1 junction in HIV-1 Gag is a critical protease substrate site regulating viral maturation. During HIV-1 assembly, the Gag polyprotein forms a lattice structure wherein the CA-SP1 junction is sequestered within a 6-helix bundle, making it the slowest and final proteolytic cleavage event needed for maturation. Cleavage at this site enables dramatic structural rearrangements, producing the mature, infectious capsid particle. Small-molecule maturation inhibitors (e.g., Bevirimat) function by binding directly across the CA-SP1 junction, stabilizing the bundle and blocking protease-mediated cleavage. Targeting this specific junction has emerged as an attractive therapeutic approach in HIV/AIDS drug development. This site is not a receptor, enzyme, or transporter per se, but is a substrate sequence/domain within the HIV-1 polyprotein recognized by the HIV-1 protease, with pivotal biological and therapeutic relevance.

Other names

CA-SP1 sitecapsid-SP1 boundaryGag CA-SP1 junctionCA/SP1 cleavage siteCA-SP1 processing site

Inhibition of proteolytic cleavage at the CA-SP1 site prevents conversion of the immature HIV-1 Gag lattice into the mature capsid, thereby blocking viral infectivity and replication. Small molecules (maturation inhibitors) bind to the CA-SP1 junction, stabilizing the 6-helix bundle and physically hindering protease access.