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.
Biomacromolecules
; 12(9): 3252-64, 2011 Sep 12.
Article
em En
| MEDLINE
| ID: mdl-21761887
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Proteínas Recombinantes
/
HIV-1
/
Proteínas do Capsídeo
/
Multimerização Proteica
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article