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 Cited by 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: 26249341DOI: 10.1107/S1399004715009402 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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