Cargando…

The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains

Cotranslational modification of the nascent polypeptide chain is one of the first events during the birth of a new protein. In eukaryotes, methionine aminopeptidases (MetAPs) cleave off the starter methionine, whereas N-acetyl-transferases (NATs) catalyze N-terminal acetylation. MetAPs and NATs comp...

Descripción completa

Detalles Bibliográficos
Autores principales: Knorr, Alexandra G., Mackens-Kiani, Timur, Musial, Joanna, Berninghausen, Otto, Becker, Thomas, Beatrix, Birgitta, Beckmann, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118133/
https://www.ncbi.nlm.nih.gov/pubmed/37079644
http://dx.doi.org/10.1371/journal.pbio.3001995
_version_ 1785028742321537024
author Knorr, Alexandra G.
Mackens-Kiani, Timur
Musial, Joanna
Berninghausen, Otto
Becker, Thomas
Beatrix, Birgitta
Beckmann, Roland
author_facet Knorr, Alexandra G.
Mackens-Kiani, Timur
Musial, Joanna
Berninghausen, Otto
Becker, Thomas
Beatrix, Birgitta
Beckmann, Roland
author_sort Knorr, Alexandra G.
collection PubMed
description Cotranslational modification of the nascent polypeptide chain is one of the first events during the birth of a new protein. In eukaryotes, methionine aminopeptidases (MetAPs) cleave off the starter methionine, whereas N-acetyl-transferases (NATs) catalyze N-terminal acetylation. MetAPs and NATs compete with other cotranslationally acting chaperones, such as ribosome-associated complex (RAC), protein targeting and translocation factors (SRP and Sec61) for binding sites at the ribosomal tunnel exit. Yet, whereas well-resolved structures for ribosome-bound RAC, SRP and Sec61, are available, structural information on the mode of ribosome interaction of eukaryotic MetAPs or of the five cotranslationally active NATs is only available for NatA. Here, we present cryo-EM structures of yeast Map1 and NatB bound to ribosome-nascent chain complexes. Map1 is mainly associated with the dynamic rRNA expansion segment ES27a, thereby kept at an ideal position below the tunnel exit to act on the emerging substrate nascent chain. For NatB, we observe two copies of the NatB complex. NatB-1 binds directly below the tunnel exit, again involving ES27a, and NatB-2 is located below the second universal adapter site (eL31 and uL22). The binding mode of the two NatB complexes on the ribosome differs but overlaps with that of NatA and Map1, implying that NatB binds exclusively to the tunnel exit. We further observe that ES27a adopts distinct conformations when bound to NatA, NatB, or Map1, together suggesting a contribution to the coordination of a sequential activity of these factors on the emerging nascent chain at the ribosomal exit tunnel.
format Online
Article
Text
id pubmed-10118133
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-101181332023-04-21 The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains Knorr, Alexandra G. Mackens-Kiani, Timur Musial, Joanna Berninghausen, Otto Becker, Thomas Beatrix, Birgitta Beckmann, Roland PLoS Biol Short Reports Cotranslational modification of the nascent polypeptide chain is one of the first events during the birth of a new protein. In eukaryotes, methionine aminopeptidases (MetAPs) cleave off the starter methionine, whereas N-acetyl-transferases (NATs) catalyze N-terminal acetylation. MetAPs and NATs compete with other cotranslationally acting chaperones, such as ribosome-associated complex (RAC), protein targeting and translocation factors (SRP and Sec61) for binding sites at the ribosomal tunnel exit. Yet, whereas well-resolved structures for ribosome-bound RAC, SRP and Sec61, are available, structural information on the mode of ribosome interaction of eukaryotic MetAPs or of the five cotranslationally active NATs is only available for NatA. Here, we present cryo-EM structures of yeast Map1 and NatB bound to ribosome-nascent chain complexes. Map1 is mainly associated with the dynamic rRNA expansion segment ES27a, thereby kept at an ideal position below the tunnel exit to act on the emerging substrate nascent chain. For NatB, we observe two copies of the NatB complex. NatB-1 binds directly below the tunnel exit, again involving ES27a, and NatB-2 is located below the second universal adapter site (eL31 and uL22). The binding mode of the two NatB complexes on the ribosome differs but overlaps with that of NatA and Map1, implying that NatB binds exclusively to the tunnel exit. We further observe that ES27a adopts distinct conformations when bound to NatA, NatB, or Map1, together suggesting a contribution to the coordination of a sequential activity of these factors on the emerging nascent chain at the ribosomal exit tunnel. Public Library of Science 2023-04-20 /pmc/articles/PMC10118133/ /pubmed/37079644 http://dx.doi.org/10.1371/journal.pbio.3001995 Text en © 2023 Knorr et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Short Reports
Knorr, Alexandra G.
Mackens-Kiani, Timur
Musial, Joanna
Berninghausen, Otto
Becker, Thomas
Beatrix, Birgitta
Beckmann, Roland
The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
title The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
title_full The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
title_fullStr The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
title_full_unstemmed The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
title_short The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
title_sort dynamic architecture of map1- and natb-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains
topic Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118133/
https://www.ncbi.nlm.nih.gov/pubmed/37079644
http://dx.doi.org/10.1371/journal.pbio.3001995
work_keys_str_mv AT knorralexandrag thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT mackenskianitimur thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT musialjoanna thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT berninghausenotto thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT beckerthomas thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT beatrixbirgitta thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT beckmannroland thedynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT knorralexandrag dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT mackenskianitimur dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT musialjoanna dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT berninghausenotto dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT beckerthomas dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT beatrixbirgitta dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains
AT beckmannroland dynamicarchitectureofmap1andnatbribosomecomplexescoordinatesthesequentialmodificationsofnascentpolypeptidechains