Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases

Woo Suk Choi, Byung Cheon Jeong, Yoo Jin Joo, Myeong Ryeol Lee, Joon Kim, Michael J. Eck, Hyun Kyu Song

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111 Citations (Scopus)


The N-end rule pathway is a regulated proteolytic system that targets proteins containing destabilizing N-terminal residues (N-degrons) for ubiquitination and proteasomal degradation in eukaryotes. The N-degrons of type 1 substrates contain an N-terminal basic residue that is recognized by the UBR box domain of the E3 ubiquitin ligase UBR1. We describe structures of the UBR box of Saccharomyces cerevisiae UBR1 alone and in complex with N-degron peptides, including that of the cohesin subunit Scc1, which is cleaved and targeted for degradation at the metaphase-anaphase transition. The structures reveal a previously unknown protein fold that is stabilized by a novel binuclear zinc center. N-terminal arginine, lysine or histidine side chains of the N-degron are coordinated in a multispecific binding pocket. Unexpectedly, the structures together with our in vitro biochemical and in vivo pulse-chase analyses reveal a previously unknown modulation of binding specificity by the residue at position 2 of the N-degron.

Original languageEnglish
Pages (from-to)1175-1181
Number of pages7
JournalNature Structural and Molecular Biology
Issue number10
Publication statusPublished - 2010 Oct

Bibliographical note

Funding Information:
We thank the staff at the 4A and 6B beamlines, Pohang Accelerator Laboratory, Korea, and the NW12 beamline, Photon Factory, Japan, for help with the data collection. We also thank Y.T. Kwon (University of Pittsburgh) for providing us with unpublished data of UBR fragments and A. Varshavsky (California Institute of Technology) for yeast strains and plasmids used for the in vivo study. This work was supported by a Basic Science Research Program through the National Research Foundation of Korea (NRF 2007-0055395), the 21C Frontier Functional Proteomics Project (FPR08B2-270), World-Class University Project (R33-10108), the Plant Signaling Network Research Center and the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092006).

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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