Catalysis and Binding of Cyclophilin A with Different HIV-1 Capsid Constructs†

Daryl A. Bosco, Dorothee Kern
2004 Biochemistry  
The prolyl isomerase cyclophilin A (CypA) is required for efficient HIV-1 replication and is incorporated into virions through a binding interaction at the Gly-Pro 222 bond located within the capsid domain of the HIV-1 Gag precursor polyprotein (Pr gag ). It has recently been shown that CypA efficiently catalyzes the cis/trans isomerization of Gly-Pro 222 within the isolated N-terminal domain of capsid (CA N ). To address the proposal that CypA interacts with Gly-Pro sequences in the C-terminal
more » ... s in the C-terminal domain of a mature capsid, the interaction between CypA and the natively folded, full-length capsid protein (CA FL ) has been investigated here using nuclear magnetic resonance spectroscopy. In addition, a fragment of the Pr gag protein encoding the full-matrix protein and the N-terminal domain of capsid (MA-CA N ) has been used to probe the catalytic interaction between CypA and an immature form of the capsid. The results discussed herein strongly suggest that Gly-Pro 222 located within the N-terminal domain of the capsid is the preferential site for CypA binding and catalysis and that catalysis of Gly-Pro 222 is unaffected by maturational processing at the N-terminus of the capsid.
doi:10.1021/bi049841z pmid:15147195 fatcat:llng4tcx6vajvl7hwoz4wla7ru