Vitamin B12 transporter BtuB (BtuB) (BtuB)

Vitamin B12 transporter BtuB is a 22-stranded beta-barrel protein located in the outer membrane of Escherichia coli [1]. Its primary biological function is the high-affinity binding and active transport of vitamin B12 (cobalamin) from the environment into the periplasmic space [1, 3]. This process is energy-dependent, relying on the TonB-ExbB-ExbD complex to provide the necessary force to unfold the protein's internal plug domain [3, 4]. Beyond its role in nutrient acquisition, BtuB serves as a critical entry point for several lethal agents, including colicins (A, E1, E2, E3) and bacteriophages like BF23 [1, 2]. Because of its ability to transport large molecules, BtuB is being investigated as a target for Trojan horse antibiotic delivery, where drugs like peptide nucleic acids (PNAs) are conjugated to vitamin B12 to bypass the bacterial outer membrane barrier [4]. Targeting BtuB offers a strategy to overcome the low permeability of the Gram-negative cell envelope, which is a major driver of antibiotic resistance [4]. The protein's expression is tightly regulated by a B12-responsive riboswitch in the 5' untranslated region of its mRNA, ensuring efficient resource management [3]. Structural studies have revealed that calcium ions are essential for high-affinity ligand binding, stabilizing the extracellular loops in a competent conformation [1, 3]. Overall, BtuB represents a versatile target for both direct antimicrobial action via bacteriocins and as a gateway for novel therapeutic conjugates [2, 4].

Other names

Cobalamin receptorCobalamin outer membrane transporterVitamin B12 receptorOuter membrane cobalamin translocator

BtuB facilitates the active transport of vitamin B12 across the outer membrane by utilizing the proton motive force transmitted via the TonB-ExbB-ExbD complex [1, 3]. It also acts as a receptor that is hijacked by colicins and bacteriophages to gain entry into the bacterial cell [2].