Catalysis and binding of cyclophilin A with different HIV-1 capsid constructs

Biochemistry. 2004 May 25;43(20):6110-9. doi: 10.1021/bi049841z.


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 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.

MeSH terms

  • Amino Acid Sequence
  • Capsid / chemistry*
  • Capsid / metabolism*
  • Cyclophilin A / chemistry
  • Cyclophilin A / metabolism*
  • Gene Products, gag / chemistry*
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism*
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Virus Replication / physiology


  • Gene Products, gag
  • Cyclophilin A