Extended Data Fig. 7: Structural comparison and representative stereo views of the crystallographic model of MYCBP2(cat).

a, Wide-field view. Regions are distinguished by colour in the stick representation: RING domain (blue), linker helix (purple), helix–turn–helix motif (green) and tandem-cysteine domain (orange). The mesh represents the experimental 2|F_obs|−|F_calc| electron density map contoured at 1.5σ. C4572 is the downstream catalytic cysteine residue in the esterification site. The mediator loop region is formed between A4518 and G4527 and is disordered in the structure. b, Close up of the mediator loop region. c, Close up of the esterification site. T4380 motif from the symmetry-related molecule (T4380(sym)) is shown and represented in grey ball and stick. d, Superposition of MYCBP2 RING domain with the RING domain from the canonical RING E3 ligase RNF4¹⁶, and from the RBR E3 ligase HOIP¹⁸. e, The linker helix and helix–turn–helix motif that connect the RING domain to the tandem cysteine domain. f, Diagram depicting the Zn coordination network for the tandem cysteine domain. Catalytic residues (numbered) are distributed throughout the tandem cysteine polypeptide. g, The tandem cysteine domain that confers threonine specificity is present in all MYCBP2 orthologues. All residues shown to be required for threonine esterification activity are conserved. Asterisks correspond to Zn-binding residues, grey arrows correspond to β-strands, gold rectangles correspond to 3₁₀-helices, and the red cylinder corresponds to an α-helix.