4UF3

Deerpox virus DPV022 in complex with Bim BH3

Summary for 4UF3

• Entry DOI: 10.2210/pdb4uf3/pdb
• Related: 4UF1 4UF2
• Descriptor: Antiapoptotic membrane protein, Bcl-2-like protein 11 (3 entities in total)
• Functional Keywords: viral protein, dpv022, deerpox virus, apoptosis, bcl-2, bim bh3
• Biological source: Deerpox virus (strain W-1170-84) (DPV); More
• Cellular location: Endomembrane system ; Peripheral membrane protein . Isoform BimEL: Mitochondrion. Isoform BimL: Mitochondrion. Isoform BimS: Mitochondrion. Isoform Bim-alpha1: Mitochondrion: O43521
• Total number of polymer chains: 2
• Total formula weight: 22907.96

Authors

Burton, D.R.,Kvansakul, M. (deposition date: 2014-12-23, release date: 2015-08-05, Last modification date: 2024-05-08)

Primary citation

Burton, D.R.,Caria, S.,Marshall, B.,Barry, M.,Kvansakul, M.
Structural Basis of Deerpox Virus-Mediated Inhibition of Apoptosis.
Acta Crystallogr.,Sect.D, 71:1593-, 2015

PubMed Abstract: Apoptosis is a key innate defence mechanism to eliminate virally infected cells. To counteract premature host-cell apoptosis, poxviruses have evolved numerous molecular strategies, including the use of Bcl-2 proteins, to ensure their own survival. Here, it is reported that the Deerpox virus inhibitor of apoptosis, DPV022, only engages a highly restricted set of death-inducing Bcl-2 proteins, including Bim, Bax and Bak, with modest affinities. Structural analysis reveals that DPV022 adopts a Bcl-2 fold with a dimeric domain-swapped topology and binds pro-death Bcl-2 proteins via two conserved ligand-binding grooves found on opposite sides of the dimer. Structures of DPV022 bound to Bim, Bak and Bax BH3 domains reveal that a partial obstruction of the binding groove is likely to be responsible for the modest affinities of DPV022 for BH3 domains. These findings reveal that domain-swapped dimeric Bcl-2 folds are not unusual and may be found more widely in viruses. Furthermore, the modest affinities of DPV022 for pro-death Bcl-2 proteins suggest that two distinct classes of anti-apoptotic viral Bcl-2 proteins exist: those that are monomeric and tightly bind a range of death-inducing Bcl-2 proteins, and others such as DPV022 that are dimeric and only bind a very limited number of death-inducing Bcl-2 proteins with modest affinities.

PubMed: 26249341
DOI: 10.1107/S1399004715009402

Experimental method

X-RAY DIFFRACTION (2.7 Å)