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TitleThe N Terminus of the Vaccinia Virus Protein F1L Is an Intrinsically Unstructured Region That Is Not Involved in Apoptosis Regulation.
Journal, issue, pagesJ Biol Chem, Vol. 291, Issue 28, Page 14600-14608, Year 2016
Publish dateJul 8, 2016
AuthorsSofia Caria / Bevan Marshall / Robyn-Lee Burton / Stephanie Campbell / Delara Pantaki-Eimany / Christine J Hawkins / Michele Barry / Marc Kvansakul /
PubMed AbstractSubversion 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 ...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.
External linksJ Biol Chem / PubMed:27151220 / PubMed Central
MethodsSAS (X-ray synchrotron)
Structure data

SASDBV4:
Vaccinia virus MVA F1L antiapoptotic Bcl-2 viral protein
Method: SAXS/SANS

Source
  • Vaccinia virus

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