PXD019846-1

PXD019846 is an original dataset announced via ProteomeXchange.

Title	Reciprocal growth control by competitive binding of nucleotide second messengers to a metabolic switch in Caulobacter crescentus
Description	Bacteria use a range of small signaling molecules to tune their physiology in response to changes in the environment. It has remained unclear if these regulatory networks operate independently or if they interact to optimize bacterial growth and survival. Here, we demonstrate that (p)ppGpp and c-di-GMP reciprocally regulate growth of Caulobacter crescentus by converging on a single small-molecule-binding protein, SmbA. Both second messengers bind to SmbA with high affinity and in a competitive manner, with the guanine moiety of (p)ppGpp and one of the guanyl bases of dimeric c-di-GMP forming identical interactions with SmbA. While c-di-GMP binding inhibits SmbA, (p)ppGpp interferes with this inhibition to sustain SmbA activity. We demonstrate that (p)ppGpp specifically promotes Caulobacter growth on glucose, while c-di-GMP inhibits glucose consumption. We find that SmbA contributes to this metabolic switch and promotes growth on glucose by quenching redox stress under these conditions. The identification of the first effector protein that acts as a central regulatory hub for two global second messengers opens up future studies on specific cross-talk between small-molecule-based regulatory networks.
HostingRepository	PRIDE
AnnounceDate	2020-12-08
AnnouncementXML	Submission_2020-12-07_22:43:24.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD019846
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Thomas Bock
SpeciesList	scientific name: Caulobacter vibrioides NA1000; NCBI TaxID: 565050;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-17 15:40:48	ID requested
⏵ 1	2020-12-07 22:43:25	announced
2	2024-10-22 05:16:23	announced	2024-10-22: Updated project metadata.

Shyp V, Dubey BN, B, ö, hm R, Hartl J, Nesper J, Vorholt JA, Hiller S, Schirmer T, Jenal U, Reciprocal growth control by competitive binding of nucleotide second messengers to a metabolic switch in Caulobacter crescentus. Nat Microbiol, 6(1):59-72(2021) [pubmed]

submitter keyword: ppGpp, c-di-GMP, glucose metabolism, adaptation

Alexander Schmidt
contact affiliation	Proteomics Core Facility Biozentrum, University of Basel Klingelbergstrasse 50/70 CH-4056 Basel / Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Thomas Bock
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	thomas.bock@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019846
     1. Label: PRIDE project
     2. Name: Reciprocal growth control by competitive binding of nucleotide second messengers to a metabolic switch in Caulobacter crescentus