Crystal structures of the sheeppox virus encoded inhibitor of apoptosis SPPV14 bound to the proapoptotic BH3 peptides Hrk and Bax

Chathura D. Suraweera, Denis R. Burton, Mark G. Hinds, Marc Kvansakul

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5 Citations (Scopus)

Abstract

Programmed death of infected cells is used by multicellular organisms to counter viral infections. Sheeppox virus encodes for SPPV14, a potent inhibitor of Bcl-2-mediated apoptosis. We reveal the structural basis of apoptosis inhibition by determining crystal structures of SPPV14 bound to BH3 motifs of proapoptotic Bax and Hrk. The structures show that SPPV14 engages BH3 peptides using the canonical ligand-binding groove. Unexpectedly, Arg84 from SPPV14 forms an ionic interaction with the conserved Asp in the BH3 motif in a manner that replaces the canonical ionic interaction seen in almost all host Bcl-2:BH3 motif complexes. These results reveal the flexibility of virus-encoded Bcl-2 proteins to mimic key interactions from endogenous host signalling pathways to retain BH3 binding and prosurvival functionality.

Original languageEnglish
Pages (from-to)2016-2026
Number of pages11
JournalFEBS Letters
Volume594
Issue number12
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

Keywords

  • apoptosis
  • Bcl-2
  • isothermal titration calorimetry
  • poxvirus
  • sheeppox virus
  • X-ray crystallography

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