NAC guides a ribosomal multienzyme complex for nascent protein processing.

Autor: Lentzsch AM; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA., Yudin D; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland., Gamerdinger M; Department of Biology, Molecular Microbiology, University of Konstanz, Konstanz, Germany., Chandrasekar S; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA., Rabl L; Department of Biology, Molecular Microbiology, University of Konstanz, Konstanz, Germany., Scaiola A; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland., Deuerling E; Department of Biology, Molecular Microbiology, University of Konstanz, Konstanz, Germany., Ban N; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland. ban@mol.biol.ethz.ch., Shan SO; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA. sshan@caltech.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Sep; Vol. 633 (8030), pp. 718-724. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1038/s41586-024-07846-7
Abstrakt: Approximately 40% of the mammalian proteome undergoes N-terminal methionine excision and acetylation, mediated sequentially by methionine aminopeptidase (MetAP) and N-acetyltransferase A (NatA), respectively 1 . Both modifications are strictly cotranslational and essential in higher eukaryotic organisms 1 . The interaction, activity and regulation of these enzymes on translating ribosomes are poorly understood. Here we perform biochemical, structural and in vivo studies to demonstrate that the nascent polypeptide-associated complex 2,3 (NAC) orchestrates the action of these enzymes. NAC assembles a multienzyme complex with MetAP1 and NatA early during translation and pre-positions the active sites of both enzymes for timely sequential processing of the nascent protein. NAC further releases the inhibitory interactions from the NatA regulatory protein huntingtin yeast two-hybrid protein K 4,5 (HYPK) to activate NatA on the ribosome, enforcing cotranslational N-terminal acetylation. Our results provide a mechanistic model for the cotranslational processing of proteins in eukaryotic cells.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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