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

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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
Volume17
Issue number10
DOIs
Publication statusPublished - 2010 Oct 1

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Ligases
Ubiquitin
Anaphase
Ubiquitin-Protein Ligases
Ubiquitination
Metaphase
Eukaryota
Histidine
Lysine
Saccharomyces cerevisiae
Arginine
Zinc
Proteins
Peptides
In Vitro Techniques
cohesins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases. / Choi, Woo Suk; Jeong, Byung Cheon; Joo, Yoo Jin; Lee, Myeong Ryeol; Kim, Joon; Eck, Michael J.; Song, Hyun Kyu.

In: Nature Structural and Molecular Biology, Vol. 17, No. 10, 01.10.2010, p. 1175-1181.

Research output: Contribution to journalArticle

Choi, Woo Suk ; Jeong, Byung Cheon ; Joo, Yoo Jin ; Lee, Myeong Ryeol ; Kim, Joon ; Eck, Michael J. ; Song, Hyun Kyu. / Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases. In: Nature Structural and Molecular Biology. 2010 ; Vol. 17, No. 10. pp. 1175-1181.
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AU - Kim, Joon

AU - Eck, Michael J.

AU - Song, Hyun Kyu

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