Extended Data Fig. 8: Overall sequence conservation in binding residues for each of the four common helices, combining information from the three different de novo-designed IL-2 mimics. | Nature

Extended Data Fig. 8: Overall sequence conservation in binding residues for each of the four common helices, combining information from the three different de novo-designed IL-2 mimics.

From: De novo design of potent and selective mimics of IL-2 and IL-15

Extended Data Fig. 8

Sequence logos were generated using combined data from binding experiments (using the heterodimeric mouse IL-2Rβγc, see Methods) from 3 independent SSM mutagenesis libraries for G2_neo2_40_1F_seq27, G2_neo2_40_1F_seq29 and G2_neo2_40_1F_seq36 (Supplementary Figs. 8–10). All of these proteins are functional high-affinity mimetics of mouse and human IL-2 (see Supplementary Figs. 6–11), some having topologies that differ from that of Neo-2/15, but all containing the four Helices H1, H3, H2′ and H4. The logos show the combined information for each helix independently. Below each logo, a line graph shows the probability score (higher means more conserved) for each amino acid in the Neo-2/15 sequence. The red line highlights positions where the Neo-2/15 amino acid has a probability score ≥30% (that is, these amino acids contribute more generally to receptor binding as they are globally enriched in the binding populations across all of the de novo IL-2 mimics tested). The topology of each helix in Neo-2/15 is shown left of each logo. The sequences of the Neo-2/15 helices and those of the corresponding helices (structurally aligned) in human IL-2 and IL-15 are shown below the graphs, highlighting the distinctiveness of the Neo-2/15 helices and binding interfaces.