7P33

Epstein-Barr virus encoded Bcl-2 homolog BHRF-1 in complex with Bid BH3 peptide

Summary for 7P33

• Entry DOI: 10.2210/pdb7p33/pdb
• Descriptor: Apoptosis regulator BHRF1, BH3-interacting domain death agonist p15, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: gamma herpes virus, epstein-barr virus, bhrf-1, bcl-2, apoptosis
• Biological source: Epstein-Barr virus (strain B95-8) (HHV-4, Human herpesvirus 4); More
• Total number of polymer chains: 10
• Total formula weight: 117864.43

Authors

Suraweera, C.D.,Hinds, M.G.,Kvansakul, M. (deposition date: 2021-07-07, release date: 2022-07-20, Last modification date: 2024-01-31)

Primary citation

Suraweera, C.D.,Hinds, M.G.,Kvansakul, M.
Crystal Structures of Epstein-Barr Virus Bcl-2 Homolog BHRF1 Bound to Bid and Puma BH3 Motif Peptides.
Viruses, 14:-, 2022

PubMed Abstract: Apoptosis is a powerful defense mechanism used by multicellular organisms to counteract viral infection. In response to premature host cell suicide, viruses have evolved numerous countermeasures to ensure cell viability to optimize their replication by encoding proteins homologous in structure and function to cellular pro-survival Bcl-2 proteins. Epstein-Barr virus (EBV), a member of the , encodes the Bcl-2 homolog BHRF1, a potent inhibitor of Bcl-2-mediated apoptosis. BHRF1 acts by directly targeting Bid and Puma, two proapoptotic proteins of the Bcl-2 family. Here, we determined the crystal structures of BHRF1 bound to peptides spanning the Bcl-2 binding motifs (Bcl-2 homology 3 motif, BH3) of Bid and Puma. BHRF1 engages BH3 peptides using the canonical ligand-binding groove of its Bcl-2 fold and maintains a salt bridge between an Arg residue with a conserved Asp residue in the BH3 motif mimicking the canonical ionic interaction seen in host Bcl-2:BH3 motif complexes. Furthermore, both Bid and Puma utilize a fifth binding pocket in the canonical ligand binding groove of BHRF1 to provide an additional hydrophobic interaction distinct from the interactions previously seen with Bak and Bim. These findings provide a structural basis for EBV-mediated suppression of host cell apoptosis and reveal the flexibility of virus encoded Bcl-2 proteins in mimicking key interactions from the endogenous host signaling pathways.

PubMed: 36298777
DOI: 10.3390/v14102222

Experimental method

X-RAY DIFFRACTION (2.78542723478 Å)