title: Larger helical populations in peptides derived from the dimerization helix of the capsid protein of HIV-1 results in peptide binding toward regions other than the "hotspot" interface.
abstract: The C-terminal domain (CTD) of the capsid protein (CA) of HIV-1 participates both in the formation of CA hexamers and in the joining of hexamers through homodimerization to form the viral capsid. Intact CA and the CTD are able to homodimerize with similar affinity (~15 μM); CTD homodimerization involves mainly an α-helical region. We have designed peptides derived from that helix with predicted higher helical propensities than the wild-type sequence while keeping residues important for dimerization. These peptides showed a higher helicity than that of the wild-type peptide, although not as high as theoretically predicted, and proved to be able to self-associate with apparent affinities similar to that of the whole CTD. However, binding to CTD mainly occurs at the last helical region of the protein. Accordingly, most of those peptides are unable to inhibit CA polymerization in vitro. Therefore, there is a subtle tuning between monomer-monomer interactions important for CTD dimerization and the maximal helical content achieved by the wild-type sequence of the interface.
authors.affiliation: Instituto de Biología Molecular y Celular, Universidad Miguel Hernández, Elche (Alicante), Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Doménech
authors.forename: Rebeca
authors.initials: R
authors.lastname: Bocanegra
authors.forename: Rosario
authors.initials: R
authors.lastname: González-Muñiz
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Mateu
authors.forename: José L
authors.initials: JL
authors.lastname: Neira
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D019281:Dimerization; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary / Q000187:drug effects; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D012984:Software; D013050:Spectrometry, Fluorescence
chemical_list: D036022:Capsid Proteins; D009842:Oligopeptides; D011994:Recombinant Proteins