SASDAD8: Antiapoptotic membrane protein, (DpV84gp022) Deerpox virus

Basic information

Entry

Database: SASBDB / ID: SASDAD8

Sample

Antiapoptotic membrane protein, (DpV84gp022) Deerpox virus

• Antiapoptotic membrane protein (protein), Deerpox virus W-1170-84

• Function / homology: Poxvirus F1/C10 / Apoptosis regulator M11L like / symbiont-mediated suppression of host apoptosis / Bcl-2-like superfamily / regulation of apoptotic process / membrane / Antiapoptotic membrane protein
• Biological species: Deerpox virus W-1170-84
• Citation: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2015; Title: Structural basis of Deerpox virus-mediated inhibition of apoptosis.; Authors: Denis R Burton / Sofia Caria / Bevan Marshall / Michele Barry / Marc Kvansakul / ; 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.

Contact author

• Marc Kvansakul (La Trobe University)

Models

Sample

• Sample: Name: Antiapoptotic membrane protein, (DpV84gp022) Deerpox virus; Specimen concentration: 0.22-6.34
• Buffer: Name: HEPES / Concentration: 25.00 mM / pH: 7.5 / Composition: 150 mM NaCl

Entity #186

Type: protein / Description: Antiapoptotic membrane protein / Formula weight: 19.6 / Num. of mol.: 2 / Source: Deerpox virus W-1170-84 / References: UniProt: Q08FF8
Sequence:

MGSSHHHHHH SQDMEAAIEF DEIVKKLLNI YINDICTTGE KRLLNNYEKS ILDRIYKSCE YIKKNYELDF NSMYNQININ DITTSDIKSK IIEALLIDSR PSVKLATLSF ISLIAEKWGE KNRAKIMEIL SNEIVEKISN NGKDFIDFID RDDDDIVDDY VLITNYLK

Experimental information

• Beam: Instrument name: Australian Synchrotron SAXS/WAXS / City: Melbourne / 国: Australia / Shape: Point / Type of source: X-ray synchrotron / Dist. spec. to detc.: 1.6 mm
• Detector: Name: Pilatus 1M

Scan

Title: Antiapoptotic membrane protein (DpV84gp022) / Measurement date: May 4, 2013 / Storage temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 30 / Unit: 1/nm /

	Min	Max
Q	0.2527	5.954

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 175 /

	Min	Max
Q	0.265615	2.51819
P(R) point	1	175
R	0	11.13

Result

Type of curve: single_conc /

	Experimental	Porod
MW	38.5 kDa	-
Volume	-	61.43 nm3

	P(R)	Guinier	Guinier error
Forward scattering, I0	0.192	0.188	0.0001
Radius of gyration, Rg	2.79 nm	2.64 nm	0.003

	Min	Max
D	-	11.1
Guinier point	4	19