Extended Data Fig. 8: Alignment of poxin proteins conserved in poxvirus representatives.
From: Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS–STING signalling
a, The poxin protein is highly conserved in mammalian poxviruses. The alignment is shaded according to conservation of physiochemical amino acid property, and numbered above according the VACV poxin amino acid sequence. The determined VACV poxin secondary structure is depicted below, active-site residues are indicated with a red dot and boxed in red, and residues that contact 2′,3′-cGAMP are boxed in orange. VACV poxin residues 195–219 are not observed in the crystal structure. Sequences depicted in alignment are as follows: VACV WR (vaccinia virus strain Western Reserve, accession YP_233066.1), VACV Cop (vaccinia virus strain Copenhagen, accession P20999.1), VACV Dryvax (vaccinia virus strain Dryvax, accession AEY73716.1), VACV ACAM2000 (vaccinia virus strain ACAM2000, accession AAQ93281.1), VACV NYVAC (vaccinia virus strain NYVAC), RPXV Utr (rabbit poxvirus strain Utrecht, accession AY484669.1), HSPV MNR76 (horsepox virus strain MNR76, accession ABH08291.1), CPXV AUS1999 (cowpox virus strain AUS1999, accession ADZ24189.1), MPXV ZAR (monkeypox virus strain Zaire-96-I-16, accession NP_536592.1), CMLV CMS (camelpox virus strain CMS, accession AAG37679.1), TATV DAH68 (taterapox virus strain Dahomey 1968, accession YP_717493.1), CPXV GER2002 (cowpox virus strain GER2002, accession ADZ30373.1), CPXV BR (cowpox virus strain Brighton Red, accession NP_619978.1), ECTV MOS (ectromelia virus strain Moscow, accession NP_671672.1), VPXV (volepox virus, accession YP_009281928.1), SKPV (skunkpox virus, accession YP_009282874.1), RCNV (raccoonpox virus, accession YP_009143488.1), YKV (yokapox virus, accession YP_004821513.1), NY_014 (NY_014 virus, accession YP_009408559.1), Murmansk (Murmansk poxvirus, accession YP_009408359.1), EPTV (Eptesipoxvirus (Eptesicus fuscus), accession YP_009408111.1), PTPV (Pteropus scapulatus, accession YP_009268718.1), Melanoplus sanguinipes (M. sanguinipes entomopox virus, accession NP_048308.1). b, Schematized alignment of poxvirus genomic DNA showing the poxin B2R–B3R locus. White boxes indicate predicted open reading frames beginning with the annotated start codons and ending with the first stop codon; deletion and nonsense mutations are shown as orange and red bars. CPXV encodes an intact poxin–schlafen fusion protein, whereas the VACV genome contains a stop codon immediately following the poxin coding region and a frameshift mutation in the schlafen (B3R) gene. Poxin is inactivated in MVA and VARV by serial mutation.
