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TitleControl of transcription elongation and DNA repair by alarmone ppGpp.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 5, Page 600-607, Year 2023
Publish dateMar 30, 2023
AuthorsJacob W Weaver / Sergey Proshkin / Wenqian Duan / Vitaly Epshtein / Manjunath Gowder / Binod K Bharati / Elena Afanaseva / Alexander Mironov / Alexander Serganov / Evgeny Nudler /
PubMed AbstractSecond messenger (p)ppGpp (collectively guanosine tetraphosphate and guanosine pentaphosphate) mediates bacterial adaptation to nutritional stress by modulating transcription initiation. More ...Second messenger (p)ppGpp (collectively guanosine tetraphosphate and guanosine pentaphosphate) mediates bacterial adaptation to nutritional stress by modulating transcription initiation. More recently, ppGpp has been implicated in coupling transcription and DNA repair; however, the mechanism of ppGpp engagement remained elusive. Here we present structural, biochemical and genetic evidence that ppGpp controls Escherichia coli RNA polymerase (RNAP) during elongation via a specific site that is nonfunctional during initiation. Structure-guided mutagenesis renders the elongation (but not initiation) complex unresponsive to ppGpp and increases bacterial sensitivity to genotoxic agents and ultraviolet radiation. Thus, ppGpp binds RNAP at sites with distinct functions in initiation and elongation, with the latter being important for promoting DNA repair. Our data provide insights on the molecular mechanism of ppGpp-mediated adaptation during stress, and further highlight the intricate relationships between genome stability, stress responses and transcription.
External linksNat Struct Mol Biol / PubMed:36997761 / PubMed Central
MethodsEM (single particle)
Resolution2.1 - 2.42 Å
Structure data

29491

8fvr

EMDB-29491, PDB-8fvr:
CryoEM structure of E.coli transcription elongation complex
Method: EM (single particle) / Resolution: 2.42 Å

29494

8fvw

EMDB-29494, PDB-8fvw:
CryoEM structure of E.coli transcription elongation complex bound to ppGpp
Method: EM (single particle) / Resolution: 2.1 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-G4P:
GUANOSINE-5',3'-TETRAPHOSPHATE / Guanosine pentaphosphate

ChemComp-NA:
Unknown entry

Source
  • escherichia coli k-12 (bacteria)
  • escherichia coli (E. coli)
KeywordsTRANSCRIPTION/DNA/RNA / Transcription elongation / TRANSCRIPTION-DNA-RNA complex / Second messager / ppGpp / DNA repair

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