Conserved interfaces mediate multiple protein-protein interactions in a prokaryotic metabolon

ABSTRACT: Enzymes in a pathway often form metabolons through weak protein-protein interactions (PPI) that localize and protect labile metabolites. Due to their transient nature, the structural architecture of these enzyme assemblies has largely remained elusive, limiting our abilities to re-engineer novel metabolic pathways. Here we delineate a complete PPI map of 1225 interactions in the E. coli 1-carbon metabolism pathway using bimolecular fluorescence complementation that can capture transient interactions in vivo and show strong intra- and inter- pathway clusters within the folate and purine biosynthesis pathways. Scanning mutagenesis experiments along with AlphaFold predictions and meta-dynamics simulations reveal that most proteins use conserved "dedicated" interfaces distant from their active

SUBMITTER: Sanchari Bhattacharyya 

PROVIDER: S-SCDT-10_1038-S44320-025-00139-9 | biostudies-other |

REPOSITORIES: biostudies-other