한빛사 논문
Woo Suk Choi 1, Byung-Cheon Jeong 1, Yoo Jin Joo 1, Myeong-Ryeol Lee 1, Joon Kim 1, Michael J Eck 2,3 & Hyun Kyu Song 1,*
1School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Korea.
2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA.
3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
*Correspondence should be addressed to H.K.S.
Abstract
Woo Suk Choi1, Byung-Cheon Jeong1, Yoo Jin Joo1, Myeong-Ryeol Lee1, Joon Kim1, Michael J Eck2,3 & Hyun Kyu Song1
1School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Korea. 2Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA. 3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Correspondence should be addressed to H.K.S.
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.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기