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Science 12 November 1999:
Vol. 286. no. 5443, pp. 1321 - 1326
DOI: 10.1126/science.286.5443.1321
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Research Articles

Structure of an E6AP-UbcH7 Complex: Insights into Ubiquitination by the E2-E3 Enzyme Cascade

Lan Huang, 1 Elspeth Kinnucan, 1 Guangli Wang, 3 Sylvie Beaudenon, 3 Peter M. Howley, 4 Jon M. Huibregtse, 3 Nikola P. Pavletich 12*

The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.

1 Cellular Biochemistry and Biophysics Program,
2 Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
3 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855, USA.
4 Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed.

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