Fig. 2: Structure of the IFIT2–IFIT3 heterodimer reveals a conserved interaction surface required for antiviral activity.

a, Cryo-EM density map of the mouse IFIT2–IFIT3 heterodimer. b, Structural model of the IFIT2–IFIT3 heterodimer. c, Linear model of the IFIT2–FIT3 heterodimer, with helices indicated, including helices 7–9 that are involved in the domain swap. d, Isolated IFIT2 monomer from the structure (left) and schematic of the IFIT2–IFIT3 heterodimer (right), with subdomains (SDs) indicated. The SD II domain swap, which forms a continuous superhelix with SD I and SD III, is illustrated. e, Structure (left) and cartoon (right) of RNA-bound IFIT1 (PDB 6C6K (ref. 26), highlighting the difference in SD II orientation between IFIT1 and IFIT2/3 and the importance of SD II in IFIT1 for 5’ cap binding. f, Evolutionary analyses of IFIT2 and IFIT3 across >20 rodent species, revealing codons evolving under purifying selection (red triangles, from FUBAR analysis) and positive selection (grey and black triangles, from FUBAR and PAML analyses, respectively).