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DOI	10.1073/pnas.2022756118
	Structure of Gcn1 bound to stalled and colliding 80S ribosomes
	Pochopien A.A.; Beckert B.; Kasvandik S.; Berninghausen O.; Beckmann R.; Tenson T.; Wilson D.N.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	The Gcn pathway is conserved in all eukaryotes, including mammals such as humans, where it is a crucial part of the integrated stress response (ISR). Gcn1 serves as an essential effector protein for the kinase Gcn2, which in turn is activated by stalled ribosomes, leading to phosphorylation of eIF2 and a subsequent global repression of translation. The fine-tuning of this adaptive response is performed by the Rbg2/Gir2 complex, a negative regulator of Gcn2. Despite the wealth of available biochemical data, information on structures of Gcn proteins on the ribosome has remained elusive. Here we present a cryo-electron microscopy structure of the yeast Gcn1 protein in complex with stalled and colliding 80S ribosomes. Gcn1 interacts with both 80S ribosomes within the disome, such that the Gcn1 HEAT repeats span from the P-stalk region on the colliding ribosome to the P-stalk and the A-site region of the lead ribosome. The lead ribosome is stalled in a nonrotated state with peptidyl-tRNA in the A-site, uncharged tRNA in the P-site, eIF5A in the E-site, and Rbg2/ Gir2 in the A-site factor binding region. By contrast, the colliding ribosome adopts a rotated state with peptidyl-tRNA in a hybrid A/P-site, uncharged-tRNA in the P/E-site, and Mbf1 bound adjacent to the mRNA entry channel on the 40S subunit. Collectively, our findings reveal the interaction mode of the Gcn2-activating protein Gcn1 with colliding ribosomes and provide insight into the regulation of Gcn2 activation. The binding of Gcn1 to a disome has important implications not only for the Gcn2-activated ISR, but also for the general ribosome-associated quality control pathways. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Disome; Gcn1; Ribosome; Stress; Translation
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179988
作者单位	Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, 20146, Germany; Institute of Technology, University of Tartu, Tartu, 50411, Estonia; Gene Center, University of Munich, Munich, 81377, Germany; Department of Biochemistry, University of Munich, Munich, 81377, Germany
推荐引用方式 GB/T 7714	Pochopien A.A.,Beckert B.,Kasvandik S.,et al. Structure of Gcn1 bound to stalled and colliding 80S ribosomes[J],2021,118(14).
APA	Pochopien A.A..,Beckert B..,Kasvandik S..,Berninghausen O..,Beckmann R..,...&Wilson D.N..(2021).Structure of Gcn1 bound to stalled and colliding 80S ribosomes.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Pochopien A.A.,et al."Structure of Gcn1 bound to stalled and colliding 80S ribosomes".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).