Nef surfaces: where to interfere with function.
Curr HIV Res
; 9(7): 543-51, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-22103838
ABSTRACT
The HIV-1 Nef protein is an accessory protein of 24-27 kDa mass that mediates a multitude of effector functions in infected cells. Although not essentially required for viral replication, HIV-1 Nef exhibits stimulating potential towards disease progression to AIDS and is therefore considered a pathogenic factor in retroviridae. Here we correlate sequence conservation in HIV-1 Nef with surface hydrophobicity and functionality in protein-protein interaction to identify accessible substructures on the surface of Nef that might be suitable as pharmacological target sites. Recent advances in targeting of Nef by small molecular compounds that interfere with SH3 domain binding or MHC class I down-regulation are discussed. Similarly, approaches for the use of larger molecules are introduced, such as tailored fusion proteins that simultaneously interact with multiple highly conserved sequence motifs of Nef. In addition, the design of a single domain antibody from llama that interferes with CD4 down-regulation activity and PAK2 binding is discussed. The flexibility in binding recognition is exemplarily shown for the modulation of RT-loop binding using engineered SH3 domains. The various considerations corroborate the potential of HIV-1 Nef as a promising target for the development of potent Nef inhibitors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
HIV-1
/
Produtos do Gene nef do Vírus da Imunodeficiência Humana
/
Proteínas Adaptadoras da Sinalização Shc
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Curr HIV Res
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha