7P0S

ORF virus encoded Bcl-2 homolog ORFV125 in complex with Puma BH3 peptide

Summary for 7P0S

• Entry DOI: 10.2210/pdb7p0s/pdb
• Descriptor: Apoptosis inhibitor, Bcl-2-binding component 3, isoforms 1/2 (3 entities in total)
• Functional Keywords: orf virus, bcl-2, apoptosis
• Biological source: Orf virus (ORFV); More
• Total number of polymer chains: 4
• Total formula weight: 38741.55

Authors

Suraweera, C.D.,Hinds, M.G.,Kvansakul, M. (deposition date: 2021-06-30, release date: 2022-07-13, Last modification date: 2024-11-13)

Primary citation

Suraweera, C.D.,Hinds, M.G.,Kvansakul, M.
Structural Investigation of Orf Virus Bcl-2 Homolog ORFV125 Interactions with BH3-Motifs from BH3-Only Proteins Puma and Hrk.
Viruses, 13:-, 2021

PubMed Abstract: Numerous viruses have evolved sophisticated countermeasures to hijack the early programmed cell death of host cells in response to infection, including the use of proteins homologous in sequence or structure to Bcl-2. Orf virus, a member of the , encodes for the Bcl-2 homolog ORFV125, a potent inhibitor of Bcl-2-mediated apoptosis in the host. ORFV125 acts by directly engaging host proapoptotic Bcl-2 proteins including Bak and Bax as well as the BH3-only proteins Hrk and Puma. Here, we determined the crystal structures of ORFV125 bound to the BH3 motif of proapoptotic proteins Puma and Hrk. The structures reveal that ORFV125 engages proapoptotic BH3 motif peptides using the canonical ligand binding groove. An Arg located in the structurally equivalent BH1 region of ORFV125 forms an ionic interaction with the conserved Asp in the BH3 motif in a manner that mimics the canonical ionic interaction seen in host Bcl-2:BH3 motif complexes. These findings provide a structural basis for Orf virus-mediated inhibition of host cell apoptosis and reveal the flexibility of virus encoded Bcl-2 proteins to mimic key interactions from endogenous host signalling pathways.

PubMed: 34372579
DOI: 10.3390/v13071374

Experimental method

X-RAY DIFFRACTION (2.50315873146 Å)