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NAC guides a ribosomal multienzyme complex for nascent protein processing.
Lentzsch, Alfred M; Yudin, Denis; Gamerdinger, Martin; Chandrasekar, Sowmya; Rabl, Laurenz; Scaiola, Alain; Deuerling, Elke; Ban, Nenad; Shan, Shu-Ou.
Afiliación
  • 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.
Nature ; 633(8030): 718-724, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39169182
ABSTRACT
Approximately 40% of the mammalian proteome undergoes N-terminal methionine excision and acetylation, mediated sequentially by methionine aminopeptidase (MetAP) and N-acetyltransferase A (NatA), respectively1. Both modifications are strictly cotranslational and essential in higher eukaryotic organisms1. 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 complex2,3 (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 K4,5 (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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribosomas / Procesamiento Proteico-Postraduccional / Chaperonas Moleculares / Metionina / Complejos Multienzimáticos Límite: Animals / Humans Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribosomas / Procesamiento Proteico-Postraduccional / Chaperonas Moleculares / Metionina / Complejos Multienzimáticos Límite: Animals / Humans Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido