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Cross-linking mass spectrometry identifies interacting regions between VACV A46 and human MAL or MyD88

ABSTRACT: Vaccinia virus immunomodulator A46 is a member of the poxviral Bcl-2-like protein family that inhibits the cellular innate immune response at the level of the TIR domain-containing TLR adaptor proteins MAL, MyD88, TRAM and TRIF. The mechanism of interaction of A46 with its targets has remained unclear. We used BS3 and EDC + sulfo-NHS to cross-link A46 to the TIR domains of MAL and MyD88 to help identify interacting residues and regions.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Vaccinia Virus

SUBMITTER: Dorothea Anrather

LAB HEAD: Tim Skern

PROVIDER: PXD018786 | Pride | 2020-10-02

REPOSITORIES: Pride

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Vaccinia Virus Immunomodulator A46: Destructive Interactions with MAL and MyD88 Shown by Negative-Stain Electron Microscopy.

Azar Daniel F DF Haas Meryl M Fedosyuk Sofiya S Rahaman Md Habibur MH Hedger Andrew A Kobe Bostjan B Skern Tim T

Structure (London, England : 1993) 20201008 12

Vaccinia virus A46 is an anti-inflammatory and non-anti-apoptotic, two-domain member of the poxviral Bcl-2-like protein family that inhibits the cellular innate immune response at the level of the Toll/interleukin-1 receptor (TIR) domain-containing TLR adaptor proteins MAL, MyD88, TRAM, and TRIF. The mechanism of interaction of A46 with its targets has remained unclear. The TIR domains of MAL and MyD88 have been shown to signal by forming filamentous assemblies. We show a clear concentration-dep ...[more]

PMID: 33035450

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