title: Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein.
abstract: The cellular protein, cyclophilin A (CypA), is incorporated into the virion of the type 1 human immunodeficiency virus (HIV-1) via a direct interaction with the capsid domain of the viral Gag polyprotein. We demonstrate that the capsid sequence 87His-Ala-Gly-Pro-Ile-Ala92 (87HAGPIA92) encompasses the primary cyclophilin A binding site and present an X-ray crystal structure of the CypA/HAGPIA complex. In contrast to the cis prolines observed in all previously reported structures of CypA complexed with model peptides, the proline in this peptide, Pro 90, binds the cyclophilin A active site in a trans conformation. We also report the crystal structure of a complex between CypA and the hexapeptide HVGPIA, which also maintains the trans conformation. Comparison with the recently determined structures of CypA in complexes with larger fragments of the HIV-1 capsid protein demonstrates that CypA recognition of these hexapeptides involves contacts with peptide residues Ala(Val) 88, Gly 89, and Pro 90, and is independent of the context of longer sequences.
authors.affiliation: Department of Biochemistry, University of Utah, Salt Lake City 84132, USA.
authors.forename: F F
authors.initials: FF
authors.lastname: Vajdos
authors.forename: S
authors.initials: S
authors.lastname: Yoo
authors.forename: M
authors.initials: M
authors.lastname: Houseweart
authors.forename: W I
authors.initials: WI
authors.lastname: Sundquist
authors.forename: C P
authors.initials: CP
authors.lastname: Hill
mesh_terms: D001665:Binding Sites; D002213:Capsid / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015683:Gene Products, gag / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D011487:Protein Conformation; D015203:Reproducibility of Results
chemical_list: D015683:Gene Products, gag; D009842:Oligopeptides; D019696:Peptidylprolyl Isomerase