title: Catalysis and binding of cyclophilin A with different HIV-1 capsid constructs.
abstract: 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.
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454.
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Bosco
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kern
mesh_terms: D000595:Amino Acid Sequence; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism*; D021984:Cyclophilin A / Q000737:chemistry / Q000378:metabolism*; D015683:Gene Products, gag / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D014779:Virus Replication / Q000502:physiology
chemical_list: D015683:Gene Products, gag; D021984:Cyclophilin A