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TitleInhibition of SRP-dependent protein secretion by the bacterial alarmone (p)ppGpp.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 1069, Year 2022
Publish dateFeb 25, 2022
AuthorsLaura Czech / Christopher-Nils Mais / Hanna Kratzat / Pinku Sarmah / Pietro Giammarinaro / Sven-Andreas Freibert / Hanna Folke Esser / Joanna Musial / Otto Berninghausen / Wieland Steinchen / Roland Beckmann / Hans-Georg Koch / Gert Bange /
PubMed AbstractThe stringent response enables bacteria to respond to nutrient limitation and other stress conditions through production of the nucleotide-based second messengers ppGpp and pppGpp, collectively known ...The stringent response enables bacteria to respond to nutrient limitation and other stress conditions through production of the nucleotide-based second messengers ppGpp and pppGpp, collectively known as (p)ppGpp. Here, we report that (p)ppGpp inhibits the signal recognition particle (SRP)-dependent protein targeting pathway, which is essential for membrane protein biogenesis and protein secretion. More specifically, (p)ppGpp binds to the SRP GTPases Ffh and FtsY, and inhibits the formation of the SRP receptor-targeting complex, which is central for the coordinated binding of the translating ribosome to the SecYEG translocon. Cryo-EM analysis of SRP bound to translating ribosomes suggests that (p)ppGpp may induce a distinct conformational stabilization of the NG domain of Ffh and FtsY in Bacillus subtilis but not in E. coli.
External linksNat Commun / PubMed:35217658 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.4 - 3.33 Å
Structure data

12734

7o5b

EMDB-12734, PDB-7o5b:
Cryo-EM structure of a Bacillus subtilis MifM-stalled ribosome-nascent chain complex with (p)ppGpp-SRP bound
Method: EM (single particle) / Resolution: 3.33 Å

EMDB-12735:
Cryo-EM map of a Bacillus subtilis MifM-stalled ribosome-nascent chain complex with GMPPNP-SRP bound
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-13839:
Cryo-EM structure of an Escherichia coli TnaC-stalled FtsQ ribosome-nascent chain complex with GMPPNP-SRP bound
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-13840:
Cryo-EM structure of an Escherichia coli TnaC-stalled FtsQ ribosome-nascent chain complex with (p)ppGpp-SRP bound
Method: EM (single particle) / Resolution: 3.1 Å

PDB-7o9f:
Bacillus subtilis Ffh in complex with ppGpp
Method: X-RAY DIFFRACTION / Resolution: 2.51 Å

PDB-7o9g:
Escherichia coli Ffh in complex with ppGpp
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

PDB-7o9h:
Escherichia coli FtsY in complex with pppGpp
Method: X-RAY DIFFRACTION / Resolution: 2.4 Å

PDB-7o9i:
Escherichia coli Ffh in complex with pppGpp
Method: X-RAY DIFFRACTION / Resolution: 2.49 Å

Chemicals

ChemComp-G4P:
GUANOSINE-5',3'-TETRAPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-0O2:
guanosine 5'-(tetrahydrogen triphosphate) 3'-(trihydrogen diphosphate)

Source
  • bacillus subtilis subsp. subtilis str. 168 (bacteria)
  • escherichia coli (E. coli)
  • bacillus subtilis (strain 168) (bacteria)
  • escherichia coli dh5[alpha] (bacteria)
  • escherichia coli (strain k12) (bacteria)
KeywordsRIBOSOME / signal recognition particle co-translational targeting alarmones translation GTPases stress response / TRANSLATION / stringent response / targeting complex / signal recognition particle / alarmones / stress

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