NAC controls cotranslational N-terminal methionine excision in eukaryotes

• 成果类型: Article
• 署名作者: Gamerdinger, Martin; Jia, Min; Schloemer, Renate; Rabl, Laurenz; Jaskolowski, Mateusz; Khakzar, Katrin M.; Ulusoy, Zeynel; Wallisch, Annalena; Jomaa, Ahmad; Hunaeus, Gundula; Scaiola, Alain; Diederichs, Kay; Ban, Nenad; Deuerling, Elke
• 署名单位: University of Konstanz; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Konstanz
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12314
• DOI: 10.1126/science.adg3297
• 发表日期: 2023-06-01
• 页码: 1238-1243
• 关键词: protein biogenesis factors; ribosomal tunnel exit; signal-sequence; crystal-structure; aminopeptidase; complex; specificity; reveals; platform; domain

摘要

N-terminal methionine excision from newly synthesized proteins, catalyzed cotranslationally by methionine aminopeptidases (METAPs), is an essential and universally conserved process that plays a key role in cell homeostasis and protein biogenesis. However, how METAPs interact with ribosomes and how their cleavage specificity is ensured is unknown. We discovered that in eukaryotes the nascent polypeptide-associated complex (NAC) controls ribosome binding of METAP1. NAC recruits METAP1 using a long, flexible tail and provides a platform for the formation of an active methionine excision complex at the ribosomal tunnel exit. This mode of interaction ensures the efficient excision of methionine from cytosolic proteins, whereas proteins targeted to the endoplasmic reticulum are spared. Our results suggest a broader mechanism for how access of protein biogenesis factors to translating ribosomes is controlled.