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Global profiling of SRP interaction with nascent polypeptides
- Source :
- Nature. 536:219-223
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- 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. The existence of parallel co- and post-translational transport pathways, 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.
- Subjects :
- Proteomics
0301 basic medicine
Proteome
Biology
environment and public health
Ribosome
Substrate Specificity
03 medical and health sciences
Protein structure
Escherichia coli
RNA, Messenger
Signal recognition particle receptor
Signal recognition particle
Binding Sites
Multidisciplinary
Escherichia coli Proteins
Membrane Proteins
Periplasmic space
Peptidylprolyl Isomerase
Protein Structure, Tertiary
Transport protein
Cell biology
Protein Transport
RNA, Bacterial
030104 developmental biology
Membrane protein
Biochemistry
Protein Biosynthesis
Periplasm
Peptides
Bacterial outer membrane
Hydrophobic and Hydrophilic Interactions
Ribosomes
Signal Recognition Particle
Protein Binding
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 536
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....25a21dee7da990caed18a0275f065059