Fig. 1: Conservation analysis of the SPPL2 PA domains.

a Sequences of human SPPL2a, SPPL2b, and SPPL2c were aligned with Clustal Omega^48,49 and conservation mapped onto the AlphaFold^46,47 predicted surface of the N-terminal PA domain. The globular PA domains are depicted as solvent accessible surfaces. Side chains that are identical are marked in dark green, chemically closely related side chains in pale green, and loosely related side chains in yellow. The helices and loops of the catalytic domains are drawn in grey. The C-terminal domains are omitted. No highly conserved surface patches are observed in the cross-subtype analysis. b SPPL2a, SPPL2b and SPPL2c from four different mammalian species (pig, mouse, Tasmanian devil, human) were aligned and mapped onto the structures with the same color code as in (a) to identify conserved subtype specific surface patches. The conservation of SPPL2s was plotted onto the structure prediction of the respective human subtype in the cross-species comparison. Structure representations were drawn in Pymol⁶⁴. The surface residues of the individual SPPL2 proteases are highly conserved among mammalian species. c Sequences of human SPPL2a and SPPL2b were aligned and mapped onto the structures with the same color code as in (a). Human SPPL2a and SPPL2b share conserved surface residues.