SASDBV4: Vaccinia virus MVA F1L antiapoptotic Bcl-2 viral protein

Basic information

• Entry: Database: SASBDB / ID: SASDBV4

Sample

Vaccinia virus MVA F1L antiapoptotic Bcl-2 viral protein

• MVA F1L antiapoptotic Bcl-2 viral protein (protein), MVA F1L (Protein F1), Vaccinia virus

Function / homology

Function:

: / host cell mitochondrial outer membrane / : / regulation of apoptotic process / membrane

Domain/homology:

Orthopoxvirus protein F1 / Poxvirus F1/C10 / Apoptosis regulator M11L like / Bcl-2-like superfamily

Component:

Apoptosis regulator OPG045

• Biological species: Vaccinia virus
• Citation: Journal: J Biol Chem / Year: 2016; Title: The N Terminus of the Vaccinia Virus Protein F1L Is an Intrinsically Unstructured Region That Is Not Involved in Apoptosis Regulation.; Authors: Sofia Caria / Bevan Marshall / Robyn-Lee Burton / Stephanie Campbell / Delara Pantaki-Eimany / Christine J Hawkins / Michele Barry / Marc Kvansakul / ; Abstract: Subversion of host cell apoptotic responses is a prominent feature of viral immune evasion strategies to prevent premature clearance of infected cells. Numerous poxviruses encode structural and functional homologs of the Bcl-2 family of proteins, and vaccinia virus harbors antiapoptotic F1L that potently inhibits the mitochondrial apoptotic checkpoint. Recently F1L has been assigned a caspase-9 inhibitory function attributed to an N-terminal α helical region of F1L spanning residues 1-15 (1) preceding the domain-swapped Bcl-2-like domains. Using a reconstituted caspase inhibition assay in yeast we found that unlike AcP35, a well characterized caspase-9 inhibitor from the insect virus Autographa californica multiple nucleopolyhedrovirus, F1L does not prevent caspase-9-mediated yeast cell death. Furthermore, we found that deletion of the F1L N-terminal region does not impede F1L antiapoptotic activity in the context of a viral infection. Solution analysis of the F1L N-terminal regions using small angle x-ray scattering indicates that the region of F1L spanning residues 1-50 located N-terminally from the Bcl-2 fold is an intrinsically unstructured region. We conclude that the N terminus of F1L is not involved in apoptosis inhibition and may act as a regulatory element in other signaling pathways in a manner reminiscent of other unstructured regulatory elements commonly found in mammalian prosurvival Bcl-2 members including Bcl-xL and Mcl-1.

Contact author

• Sofia Caria

Models

• Model #535: ; Type: mix / Software: BUNCH / Radius of dummy atoms: 1.90 A / Chi-square value: 7.29; Search similar-shape structures of this assembly by Omokage search (details)
• Model #536: ; Type: mix / Software: CORAL / Radius of dummy atoms: 1.90 A / Chi-square value: 3.8416; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Vaccinia virus MVA F1L antiapoptotic Bcl-2 viral protein; Specimen concentration: 0.12-3.60
• Buffer: Name: 25 mM HEPES, 150 mM NaCl, 5 mM DTT / pH: 7.5

Entity #341

Name: MVA F1L (Protein F1) / Type: protein / Description: MVA F1L antiapoptotic Bcl-2 viral protein / Formula weight: 25.291 / Num. of mol.: 2 / Source: Vaccinia virus / References: UniProt: O57173
Sequence:

MGSSHHHHHH SQDPMLSMFM CNNIVDYVDG IVQDIEDEAS NNVDHDYVYP LPENMVYRFD KSTNILDYLS TERDHVMMAV RYYMSKQRLD DLYRQLPTKT RSYIDIINIY CDKVSNDYNR DMNIMYDMAS TKSFTVYDIN NEVNTILMDN KGLGVRLATI SFITELGRRC MNPVKTIKMF TLLSHTICDD CFVDYITDIS PPDNTIPNTS TREYLK

Experimental information

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

Scan

Title: Vaccinia MVA F1L antiapoptotic Bcl-2 protein / Measurement date: Apr 15, 2016 / Storage temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 18 / Unit: 1/nm /

	Min	Max
Q	0.196	5.1598

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 335 /

	Min	Max
Q	0.196003	2.34086
P(R) point	1	335
R	0	16.2

Result

D max: 16.2 / Type of curve: single_conc /

	Experimental	Porod
MW	51.7 kDa	-
Volume	-	74.36 nm3

	Guinier	P(R)
Forward scattering, I0	0.0735086	-
Radius of gyration, Rg	3.41 nm	3.68 nm