(A) Overlay of structures of the SNL domains of SidC/SdcA. Four structures were superimposed based on the Cα atoms of the main lobe. The INS lobes adopt a wide range of conformations relative to the main lobe and are colored in red (SdcA-UbcH5C complex), green (SidC 1–542, PDB ID 4TRG), blue (SidC 1–871, PDB ID 4ZUZ), and purple (SidC-UbcH7~Ub), respectively. (B) An orthogonal view of the four superimposed structures shown in surface. The INS lobes are colored with the same scheme as in (A). (C) Structural overlay of HECT domains with their N-lobes superimposed. The C-lobes are colored red (NEDD4L-UbcH5B~Ub, PDB 3JW0), blue (NEDD4~Ub, PDB 4BBN), green (E6AP-UbcH7, PDB 1D5F), and purple (Rsp5~Ub sub, PDB 4LCD), respectively. The E2 binding site is indicated by a curved dashed line. (D) Structural overlay of two HECT-like bacterial E3s. The E2-binding N-lobe is superimposed. The mobile C-lobe is colored in red (SopA-UbcH7, PDB 3SY2) and blue (NleL-UbcH7, PDB 3SQV), respectively.