EMD-36599

Single-particle
2.6 Å
EMD-36599 Deposition: 17/06/2023
Map released: 05/06/2024
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-36599

Structure of E6AP-E6 complex in Att1 state

EMD-36599

Single-particle
2.6 Å
EMD-36599 Deposition: 17/06/2023
Map released: 05/06/2024
Last modified: 05/06/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Human papillomavirus 16
Sample: E6AP-E6 complex
Fitted models: 8jrn (Avg. Q-score: 0.531)

Deposition Authors: Wang Z , Yu X
Structural insights into the functional mechanism of the ubiquitin ligase E6AP.
Wang Z , Fan F, Li Z, Ye F , Wang Q, Gao R, Qiu J, Lv Y, Lin M, Xu W, Luo C , Yu X
(2024) Nat Commun , 15 , 3531 - 3531
PUBMED: 38670961
DOI: doi:10.1038/s41467-024-47586-w
ISSN: 2041-1723
Abstract:
E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.