The hydrophobic pocket of cyclophilin is the binding site for the human immunodeficiency virus type 1 Gag polyprotein - PubMed (original) (raw)
The hydrophobic pocket of cyclophilin is the binding site for the human immunodeficiency virus type 1 Gag polyprotein
D Braaten et al. J Virol. 1997 Mar.
Abstract
Completion of an early step in the human immunodeficiency virus type 1 (HIV-1) life cycle requires incorporation into virions of the cellular peptidyl-prolyl isomerase cyclophilin A (CyPA) by the Gag polyprotein. Elucidation of the biochemical role of CyPA would be aided by a detailed analysis of the genetic requirements for the formation of the Gag-CyPA complex; previous experiments have demonstrated the requirement for a critical proline and the immediately preceding glycine, located within the capsid domain of Gag, but nothing is known about the necessary CyPA residues. Cyclophilins possess a hydrophobic pocket where proline-containing peptide substrates and the immunosuppressive drug cyclosporine A bind. In this study, we engineered five CyPA mutations, each of which alters a residue that contributes to the hydrophobic pocket. Compared with the wild-type protein, all of the mutants drastically reduced CyPA binding to HIV-1 Gag and similarly inhibited CyPA incorporation into virions. In addition, we demonstrated that previously reported differences between the Gag-binding properties of CyPA and CyPB are due to adventitious association involving residues in the signal sequence of CyPB and that the core domain of CyPB interacts with Gag in a fashion which is indistinguishable from that of CyPA. These studies indicate that, as with other proline-containing peptides or cyclosporine A, HIV-1 Gag directly contacts residues in the hydrophobic pocket of CyPA.
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References
- Science. 1984 Nov 2;226(4674):544-7 - PubMed
- Virology. 1996 Aug 1;222(1):279-82 - PubMed
- Mol Cell Biol. 1988 May;8(5):2159-65 - PubMed
- Blood. 1988 Dec;72(6):1904-10 - PubMed
- Nature. 1989 Feb 2;337(6206):476-8 - PubMed
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