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

Vander Kooi CW, Ohi MD, Rosenberg JA, Oldham ML, Newcomer ME, Gould KL, Chazin WJ
Biochemistry. 2006 45 (1): 121-30

PMID: 16388587 · PMCID: PMC2570371 · DOI:10.1021/bi051787e

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.

MeSH Terms (17)

Amino Acid Sequence Binding Sites Carrier Proteins Crystallography, X-Ray Dimerization DNA Repair Enzymes Humans Models, Chemical Molecular Sequence Data Nuclear Proteins Polyubiquitin Protein Structure, Tertiary RNA, Small Nuclear RNA Splicing Factors Substrate Specificity Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases

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