Crystal structure of the catalytic C‐lobe of the HECT‐type ubiquitin ligase E6AP

Please always quote using this URN: urn:nbn:de:bvb:20-opus-214812
  • 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 theThe 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.show moreshow less

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Metadaten
Author: Lena K. Ries, Anna K. L. Liess, Christian G. Feiler, Donald E. Spratt, Edward D. Lowe, Sonja LorenzORCiD
URN:urn:nbn:de:bvb:20-opus-214812
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):Protein Science
Year of Completion:2020
Volume:29
Issue:6
First Page:1550
Last Page:1554
Source:Protein Science 2020, 29(6):1550-1554. DOI: 10.1002/pro.3832
DOI:https://doi.org/10.1002/pro.3832
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:E3 enzyme; UBE3A; X‐ray crystallography; dimerization; domain swapping
Release Date:2021/04/16
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International