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- Title
Structural basis for the recognition of N-end rule substrates by the UBR box of ubiquitin ligases.
- Authors
Woo Suk Choi; Byung-Cheon Jeong; Yoo Jin Joo; Myeong-Ryeol Lee; Joon Kim; Eck, Michael J.; Hyun Kyu Song
- 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.
- Publication
Nature Structural & Molecular Biology, 2010, Vol 17, Issue 10, p1175
- ISSN
1545-9993
- Publication type
Academic Journal
- DOI
10.1038/nsmb.1907