Supplementary Figure 2: Intramolecular protein-protein interactions within the ZnF1–3 and ZnF4–6 clusters of Unkempt in their RNA-bound conformation.

(a) Structure of the ZnF4–6 cluster shown in a ribbon representation. ZnFs 4, 5, and 6 are colored in light blue, the N-terminal loop with α-helix 1 and the linker separating ZnFs 5 and 6 with α-helix 2 are colored in light orange, and the linker separating ZnFs 4 and 5 is colored in green. (b) Hydrophobic and hydrogen-bonding interactions of the N-terminal α-helix 1 and the loop residues (Thr209, Val212, Leu213, Tyr216 and Lys217) with the linker separating ZnFs 5 and 6 (Thr285, Phe289 and Tyr294), and with the linker separating ZnFs 4 and 5 (Asp242, Arg244 and Ser246). (c) Hydrogen-bonding interactions and van der Waals contacts of the linker separating ZnFs 4 and 5 (Arg244, Arg245, Ser246, Tyr252, Ser254 and Pro256) with the N-terminal loop and α-helix 1 (Leu213, Gly214, Tyr216 and Lys217), and with the linker between ZnFs 5 and 6 (Thr283, Glu286, Gln287, His290 and Ile293). (d) Structure-based sequence alignment of the ZnF1–3 and ZnF4–6 clusters. Cysteine and histidine residues coordinated to Zn are highlighted in blue. Secondary structure elements of ZnF1–3 and ZnF4–6 are shown above the sequences and are colored as in a and b. Residues involved in intramolecular hydrophobic interactions (rectangles) and hydrogen-bonding via their backbone functional groups (asterisks) or side chains (triangles) in both domains are color-coded for the ZnF regions, the N- and C-termini, and for the intervening linkers. (e) Structure of the ZnF1–3 cluster shown in ribbon representations. ZnFs 1, 2, and 3 are colored in light blue, the N- and C-termini and the linker separating ZnFs 2 and 3 with α-helix 3 are colored in light orange, and the linker separating ZnFs 1 and 2 is colored in green. (f) Hydrophobic and hydrogen-bonding interactions of the N-terminal α-helix 1 and loop residues (His33, Tyr36, Leu37, Phe40 and Arg41) with the linker between ZnFs 2 and 3 (Thr116, Tyr120 Tyr125), and with the linker separating ZnFs 1 and 2 (Arg71). (g) Hydrogen-bonding interactions and van der Waals contacts of the linker separating ZnFs 1 and 2 (Arg71, Arg72, Arg73, Ser74, Arg76, Tyr84, Pro86, Asp87 and Tyr89) with the N-terminal loop and α-helix 1 (Leu37, Lys38, Phe40 and Arg41), and with the linker between ZnFs 2 and 3 (Thr112, Glu117, Arg118, His121 and Tyr124). Hydrogen bonds that are equivalent between ZnF1–3 and ZnF4–6 are colored red. Cysteine and histidine side chains coordinated to Zn atoms (light blue balls) are shown in stick representation.