@article{RiesLiessFeileretal.2020,
  author    = {Ries, Lena K. and Liess, Anna K. L. and Feiler, Christian G. and Spratt, Donald E. and Lowe, Edward D. and Lorenz, Sonja},
  title     = {Crystal structure of the catalytic C-lobe of the HECT-type ubiquitin ligase E6AP},
  series = {Protein Science},
  volume    = {29},
  journal   = {Protein Science},
  number    = {6},
  doi       = {10.1002/pro.3832},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214812},
  pages     = {1550 -- 1554},
  year      = {2020},
  abstract  = {The HECT-type ubiquitin ligase E6AP (UBE3A) is critically involved in several neurodevelopmental disorders and human papilloma virus-induced cervical tumorigenesis; the structural mechanisms underlying the activity of this crucial ligase, however, are incompletely understood. Here, we report a crystal structure of the C-terminal lobe ("C-lobe") of the catalytic domain of E6AP that reveals two molecules in a domain-swapped, dimeric arrangement. Interestingly, the molecular hinge that enables this structural reorganization with respect to the monomeric fold coincides with the active-site region. While such dimerization is unlikely to occur in the context of full-length E6AP, we noticed a similar domain swap in a crystal structure of the isolated C-lobe of another HECT-type ubiquitin ligase, HERC6. This may point to conformational strain in the active-site region of HECT-type ligases with possible implications for catalysis. Significance Statement The HECT-type ubiquitin ligase E6AP has key roles in human papilloma virus-induced cervical tumorigenesis and certain neurodevelopmental disorders. Here, we present a crystal structure of the C-terminal, catalytic lobe of E6AP, providing basic insight into the conformational properties of this functionally critical region of HECT-type ligases.},
  language  = {en}
}