The Binding Interface between Human APOBEC3F and HIV-1 Vif Elucidated by Genetic and Computational Approaches

Christopher Richards, John S. Albin, Özlem Demir, Nadine M. Shaban, Elizabeth M. Luengas, Allison M. Land, Brett D. Anderson, John R. Holten, John S. Anderson, Daniel A. Harki, Rommie E. Amaro, Reuben S. Harris

Producción científica: Articlerevisión exhaustiva

31 Citas (Scopus)

Resumen

APOBEC3 family DNA cytosine deaminases provide overlapping defenses against pathogen infections. However, most viruses have elaborate evasion mechanisms such as the HIV-1 Vif protein, which subverts cellular CBF-β and a polyubiquitin ligase complex to neutralize these enzymes. Despite advances in APOBEC3 and Vif biology, a full understanding of this direct host-pathogen conflict has been elusive. We combine virus adaptation and computational studies to interrogate the APOBEC3F-Vif interface and build a robust structural model. A recurring compensatory amino acid substitution from adaptation experiments provided an initial docking constraint, and microsecond molecular dynamic simulations optimized interface contacts. Virus infectivity experiments validated a long-lasting electrostatic interaction between APOBEC3F E289 and HIV-1 Vif R15. Taken together with mutagenesis results, we propose a wobble model to explain how HIV-1 Vif has evolved to bind different APOBEC3 enzymes and, more generally, how pathogens may evolve to escape innate host defenses.

Idioma originalEnglish (US)
Páginas (desde-hasta)1781-1788
Número de páginas8
PublicaciónCell Reports
Volumen13
N.º9
DOI
EstadoPublished - dic 1 2015
Publicado de forma externa

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Huella

Profundice en los temas de investigación de 'The Binding Interface between Human APOBEC3F and HIV-1 Vif Elucidated by Genetic and Computational Approaches'. En conjunto forman una huella única.

Citar esto