@article{LorenzBhattacharyyaFeileretal.2016,
  author    = {Lorenz, Sonja and Bhattacharyya, Moitrayee and Feiler, Christian and Rape, Michael and Kuriyan, John},
  title     = {Crystal Structure of a Ube2S-Ubiquitin Conjugate},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0147550},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167265},
  pages     = {e0147550},
  year      = {2016},
  abstract  = {Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze the formation of an isopeptide linkage between the C-terminus of a "donor" ubiquitin and a primary amino group of an "acceptor" ubiquitin molecule. This reaction involves an intermediate, in which the C-terminus of the donor ubiquitin is thioester-bound to the active site cysteine of the E2 and a functionally important interface is formed between the two proteins. A docked model of a Ube2S-donor ubiquitin complex was generated previously, based on chemical shift mapping by NMR, and predicted contacts were validated in functional studies. We now present the crystal structure of a covalent Ube2S-ubiquitin complex. The structure contains an interface between Ube2S and ubiquitin in trans that resembles the earlier model in general terms, but differs in detail. The crystallographic interface is more hydrophobic than the earlier model and is stable in molecular dynamics (MD) simulations. Remarkably, the docked Ube2S-donor complex converges readily to the configuration seen in the crystal structure in 3 out of 8 MD trajectories. Since the crystallographic interface is fully consistent with mutational effects, this indicates that the structure provides an energetically favorable representation of the functionally critical Ube2S-donor interface.},
  language  = {en}
}
@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}
}