Vitamin B12-binding proteins BtuG2 and BtuH2 (BtuG2 and BtuH2)

BtuG2 and BtuH2 are specialized vitamin B12 (cobalamin) binding proteins found in the human gut commensal bacterium Bacteroides thetaiotaomicron and related Bacteroidetes. BtuG2 is a surface-exposed lipoprotein that adopts a seven-bladed beta-propeller fold and acts as a high-affinity "lid" for the TonB-dependent transporter BtuB2, capturing cobalamin from the environment with femtomolar affinity. BtuH2 is a membrane-associated protein encoded in the same genetic locus that also binds cobalamin directly and is essential for efficient vitamin acquisition and competitive fitness in the gut. These proteins allow Bacteroides to effectively compete for limited B12 resources, even "pirating" the vitamin from human intrinsic factor. Because cobalamin is a keystone micronutrient that shapes the gut microbial community, BtuG2 and BtuH2 are considered potential therapeutic targets for modulating the microbiome to treat conditions like inflammatory bowel disease or metabolic disorders. Inhibiting these proteins could selectively reduce the fitness of specific bacterial populations without the broad-spectrum effects of traditional antibiotics.

Other names

BT1954 (BtuG2)BT1956 (BtuH2)Cobalamin-binding protein BtuG2Cobalamin-binding protein BtuH2BtuG2-BtuH2 complex

Inhibition of bacterial vitamin B12 acquisition to modulate gut microbiome composition or reduce the fitness of specific commensal or pathogenic bacteria.