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] , (b) closed, ‘T’-shaped conformation of WWP1/AIP [PDB: 1ND7] , and (c) trans-thioesterification complex of NEDD4L with a ubiquitin-E2 (UbcH5B) conjugate [PDB:3JVZ] . 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.
Lorenz et al. BMC Biology 2013 11:65 doi:10.1186/1741-7007-11-65