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 metadynamics simulations reveal that most proteins use conserved "dedicated" interfaces distant from their active

SUBMITTER: Bhattacharyya S 

PROVIDER: S-EPMC12583656 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature