The Prp19 U-box crystal structure suggests a common dimeric architecture for a class of oligomeric E3 ubiquitin ligases

Craig W. Vander Kooi, Melanie D. Ohi, Joshua A. Rosenberg, Michael L. Oldham, Marcia E. Newcomer, Kathleen L. Gould, Walter J. Chazin

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Prp19 is an essential splicing factor and a member of the U-box family of E3 ubiquitin ligases. Prp19 forms a tetramer via a central coiled-coil domain. Here, we show the U-box domain of Prp19 exists as a dimer within the context of the Prp19 tetramer. A high-resolution structure of the homodimeric state of the Prp19 U-box was determined by X-ray crystallography. Mutation of the U-box dimer interface abrogates U-box dimer formation and is lethal in vivo. The structure of the U-box dimer enables construction of a complete model of Prp19 providing insights into how the tetrameric protein functions as an E3 ligase. Finally, comparison of the Prp19 U-box homodimer with the heterodimeric complex of BRCA1/BARD1 RING-finger domains uncovers a common architecture for a family of oligomeric U-box and RING-finger E3 ubiquitin ligases, which has mechanistic implications for E3 ligase-mediated polyubiquitination and E4 polyubiquitin ligases.

Original languageEnglish
Pages (from-to)121-130
Number of pages10
JournalBiochemistry
Volume45
Issue number1
DOIs
StatePublished - Jan 10 2006

ASJC Scopus subject areas

  • Biochemistry

Fingerprint

Dive into the research topics of 'The Prp19 U-box crystal structure suggests a common dimeric architecture for a class of oligomeric E3 ubiquitin ligases'. Together they form a unique fingerprint.

Cite this