Chemistry
Document Type
Article
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.
Publication Title
Protein Science
Publication Date
6-2020
Volume
29
Issue
6
First Page
1550
Last Page
1554
ISSN
0961-8368
DOI
10.1002/pro.3832
Keywords
dimerization, domain swapping, E3 enzyme, UBE3A, X-ray crystallography
Repository Citation
Ries, Lena K.; Liess, Anna K.L.; Feiler, Christian G.; Spratt, Donald E.; Lowe, Edward D.; and Lorenz, Sonja, "Crystal structure of the catalytic C-lobe of the HECT-type ubiquitin ligase E6AP" (2020). Chemistry. 148.
https://commons.clarku.edu/chemistry/148
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Conditions
Ries, L. K., Liess, A. K., Feiler, C. G., Spratt, D. E., Lowe, E. D., & Lorenz, S. (2020). Crystal structure of the catalytic C‐lobe of the HECT‐type ubiquitin ligase E6AP. Protein Science, 29(6), 1550-1554.
