7QTW

Kaposi sarcoma associated herpes virus(KSHV) encoded apoptosis inhibitor, KsBcl-2 in complex with Bid BH3

Summary for 7QTW

• Entry DOI: 10.2210/pdb7qtw/pdb
• Descriptor: Bcl-2, BH3-interacting domain death agonist p15, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: apoptosis, viral bcl-2 protein, gamma herpes virus, kaposi sarcoma virus
• Biological source: Human gammaherpesvirus 8; More
• Total number of polymer chains: 2
• Total formula weight: 20578.56

Authors

Suraweera, C.D.,Hinds, M.G.,Kvansakul, M. (deposition date: 2022-01-17, release date: 2022-11-23, Last modification date: 2024-05-01)

Primary citation

Suraweera, C.D.,Hinds, M.G.,Kvansakul, M.
Structural Insight into KsBcl-2 Mediated Apoptosis Inhibition by Kaposi Sarcoma Associated Herpes Virus.
Viruses, 14:-, 2022

PubMed Abstract: Numerous large DNA viruses have evolved sophisticated countermeasures to hijack the premature programmed cell death of host cells post-infection, including the expression of proteins homologous in sequence, structure, or function to cellular Bcl-2 proteins. Kaposi sarcoma herpes virus (KSHV), a member of the , has been shown to encode for KsBcl-2, a potent inhibitor of Bcl-2 mediated apoptosis. KsBcl-2 acts by directly engaging host pro-apoptotic Bcl-2 proteins including Bak, Bax and Bok, the BH3-only proteins; Bim, Bid, Bik, Hrk, Noxa and Puma. Here we determined the crystal structures of KsBcl-2 bound to the BH3 motif of pro-apoptotic proteins Bid and Puma. The structures reveal that KsBcl-2 engages pro-apoptotic BH3 motif peptides using the canonical ligand binding groove. Thus, the presence of the readily identifiable conserved BH1 motif sequence "NWGR" of KsBcl-2, as well as highly conserved Arg residue (R86) 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 KSHV 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: 35458468
DOI: 10.3390/v14040738

Experimental method

X-RAY DIFFRACTION (1.41 Å)