uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Global profiling of SRP interaction with nascent polypeptides
Univ Heidelberg ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.;German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany..
Univ Heidelberg ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Neuenheimer Feld 282, D-69120 Heidelberg, Germany.;German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany..
HITS gGmbH, Heidelberg Inst Theoret Studies, Schloss Wolfsbrunnenweg 35, D-69118 Heidelberg, Germany..
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Stockholm Univ, Ctr Biomembrane Res, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.;Stockholm Univ, Sci Life Lab, S-17121 Solna, Sweden..
Show others and affiliations
2016 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 536, no 7615, 219-223 p.Article in journal, Letter (Refereed) Published
Abstract [en]

Signal recognition particle (SRP) is a universally conserved protein-RNA complex that mediates co-translational protein translocation and membrane insertion by targeting translating ribosomes to membrane translocons(1). The existence of parallel co- and post-translational transport pathways(2), however, raises the question of the cellular substrate pool of SRP and the molecular basis of substrate selection. Here we determine the binding sites of bacterial SRP within the nascent proteome of Escherichia coli at amino acid resolution, by sequencing messenger RNA footprints of ribosome-nascent-chain complexes associated with SRP. SRP, on the basis of its strong preference for hydrophobic transmembrane domains (TMDs), constitutes a compartment-specific targeting factor for nascent inner membrane proteins (IMPs) that efficiently excludes signal-sequence-containing precursors of periplasmic and outer membrane proteins. SRP associates with hydrophobic TMDs enriched in consecutive stretches of hydrophobic and bulky aromatic amino acids immediately on their emergence from the ribosomal exit tunnel. By contrast with current models, N-terminal TMDs are frequently skipped and TMDs internal to the polypeptide sequence are selectively recognized. Furthermore, SRP binds several TMDs in many multi-spanning membrane proteins, suggesting cycles of SRP-mediated membrane targeting. SRP-mediated targeting is not accompanied by a transient slowdown of translation and is not influenced by the ribosome-associated chaperone trigger factor (TF), which has a distinct substrate pool and acts at different stages during translation. Overall, our proteome-wide data set of SRP-binding sites reveals the underlying principles of pathway decisions for nascent chains in bacteria, with SRP acting as the dominant triaging factor, sufficient to separate IMPs from substrates of the SecA-SecB post-translational translocation and TF-assisted cytosolic protein folding pathways.

Place, publisher, year, edition, pages
2016. Vol. 536, no 7615, 219-223 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-304216DOI: 10.1038/nature19070ISI: 000381472100038PubMedID: 27487212OAI: oai:DiVA.org:uu-304216DiVA: diva2:1034842
Funder
Swedish Research CouncilGerman Research Foundation (DFG), SFB638; FOR1805
Available from: 2016-10-13 Created: 2016-10-03 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Cell and Molecular Biology
In the same journal
Nature
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 412 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf