6TGK

Domain swapped E6AP C-lobe dimer

Summary for 6TGK

• Entry DOI: 10.2210/pdb6tgk/pdb
• Descriptor: Ubiquitin-protein ligase E3A, ACETATE ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: e6ap, swapped dimer, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 12216.88

Authors

Ries, L.K.,Feiler, C.,Lowe, L.D.,Liess, A.K.L.,Lorenz, S. (deposition date: 2019-11-16, release date: 2020-02-26, Last modification date: 2024-01-24)

Primary citation

Ries, L.K.,Liess, A.K.L.,Feiler, C.G.,Spratt, D.E.,Lowe, E.D.,Lorenz, S.
Crystal structure of the catalytic C-lobe of the HECT-type ubiquitin ligase E6AP.
Protein Sci., 29:1550-1554, 2020

PubMed 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.

PubMed: 31994269
DOI: 10.1002/pro.3832

Experimental method

X-RAY DIFFRACTION (1.3 Å)