Figure 3.

Swinging domains in HECT E3 enzymes. Cartoon representations of crystal structures of various HECT domains. (a) Open, ‘L’-shaped conformation of E6AP (E3) in complex with UbcH7 (E2) [PDB: 1C4Z] [62], (b) closed, ‘T’-shaped conformation of WWP1/AIP [PDB: 1ND7] [63], and (c) trans-thioesterification complex of NEDD4L with a ubiquitin-E2 (UbcH5B) conjugate [PDB:3JVZ] [64]. In (c) the E2 active site cysteine was mutated to serine (colored yellow in our representation), resulting in an oxy-ester linkage with ubiquitin in lieu of the native thioester. (d) Distinct classes of C-lobe orientations based on the crystal structures of various HECT domains (WWP1/AIP [PDB: 1ND7], Itch [PDB: 3TUG], HUWE1 [PDB: 3G1N, 3H1D], NEDD4L [PDB: 2ONI, 3JVZ], E6AP [PDB: 1C4Z], Rsp5 [PDB: 3OLM], Smurf2 [PDB: 1ZVD], NEDD [PDB: 2XBB]). A second unique C-lobe orientation observed for NEDD [PDB: 2XBF] could not be displayed for clarity. In our representation the HECT N-lobes are superimposed and only one of them is displayed. Binding partners, such as E2 enzymes or ubiquitin, found in some of the structures are not displayed.