Systematic mapping of protein‐metabolite interactions in central metabolism of Escherichia coli
OPEN ACCESS
Author / Producer
Date
2019-08-01
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
Abstract
Metabolite binding to proteins regulates nearly all cellular processes, but our knowledge of these interactions originates primarily from empirical in vitro studies. Here, we report the first systematic study of interactions between water‐soluble proteins and polar metabolites in an entire biological subnetwork. To test the depth of our current knowledge, we chose to investigate the well‐characterized Escherichia coli central metabolism. Using ligand‐detected NMR, we assayed 29 enzymes towards binding events with 55 intracellular metabolites. Focusing on high‐confidence interactions at a false‐positive rate of 5%, we detected 98 interactions, among which purine nucleotides accounted for one‐third, while 50% of all metabolites did not interact with any enzyme. In contrast, only five enzymes did not exhibit any metabolite binding and some interacted with up to 11 metabolites. About 40% of the interacting metabolites were predicted to be allosteric effectors based on low chemical similarity to their target's reactants. For five of the eight tested interactions, in vitro assays confirmed novel regulatory functions, including ATP and GTP inhibition of the first pentose phosphate pathway enzyme. With 76 new candidate regulatory interactions that have not been reported previously, we essentially doubled the number of known interactions, indicating that the presently available information about protein–metabolite interactions may only be the tip of the iceberg.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
15 (8)
Pages / Article No.
Publisher
EMBO Press
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Allostery; Central metabolism; Nuclear magnetic resonance; Protein-metabolite interactions; Regulation
Organisational unit
03713 - Sauer, Uwe / Sauer, Uwe
03591 - Allain, Frédéric / Allain, Frédéric