Structural basis of signal sequence surveillance and selection by the SRP-FtsY complex

Ottilie von Loeffelholz, Kèvin Knoops, Aileen Ariosa, Xin Zhang, Manikandan Karuppasamy, Karine Huard, Guy Schoehn, Imre Berger, Shu-ou Shan, Christiane Schaffitzel

Research output: Contribution to journalArticle (Academic Journal)

15 Citations (Scopus)

Abstract

Signal-recognition particle (SRP)-dependent targeting of translating ribosomes to membranes is a multistep quality-control process. Ribosomes that are translating weakly hydrophobic signal sequences can be rejected from the targeting reaction even after they are bound to the SRP. Here we show that the early complex, formed by Escherichia coli SRP and its receptor FtsY with ribosomes translating the incorrect cargo EspP, is unstable and rearranges inefficiently into subsequent conformational states, such that FtsY dissociation is favored over successful targeting. The N-terminal extension of EspP is responsible for these defects in the early targeting complex. The cryo-electron microscopy structure of this 'false' early complex with EspP revealed an ordered M domain of SRP protein Ffh making two ribosomal contacts, and the NG domains of Ffh and FtsY forming a distorted, flexible heterodimer. Our results provide a structural basis for SRP-mediated signal-sequence selection during recruitment of the SRP receptor.

Original languageEnglish
Pages (from-to)604-10
Number of pages7
JournalNature Structural and Molecular Biology
Volume20
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Bacterial Proteins
  • Cryoelectron Microscopy
  • Escherichia coli
  • Escherichia coli Proteins
  • Models, Molecular
  • Multiprotein Complexes
  • Protein Conformation
  • Protein Sorting Signals
  • Receptors, Cytoplasmic and Nuclear
  • Serine Endopeptidases
  • Signal Recognition Particle

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    von Loeffelholz, O., Knoops, K., Ariosa, A., Zhang, X., Karuppasamy, M., Huard, K., Schoehn, G., Berger, I., Shan, S., & Schaffitzel, C. (2013). Structural basis of signal sequence surveillance and selection by the SRP-FtsY complex. Nature Structural and Molecular Biology, 20(5), 604-10. https://doi.org/10.1038/nsmb.2546