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Lookup NU author(s): Dr Javier Abellon-RuizORCiD, Dr Adam HartORCiD, Emeritus Professor Robert HirtORCiD, Dr Arnaud Basle, Professor Bert van den BergORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/The acquisition of vitamin B12 and related cobamides is a key determinant for the fitness of Bacteroidota in the gut. Depending on the species, this uptake process relies on one to four transport systems centred on conserved core outer membrane (OM) complexes composed of the TonB-dependent transporter BtuB and the surface-exposed lipoprotein BtuG. Additionally, the surface-exposed lipoprotein BtuH, although not tightly associated with the BtuBG complex, contributes to cobamide uptake and provides a fitness advantage. Here, we report the functional and structural characterization of BtuJ1 from Bacteroides thetaiotaomicron (B. theta), an additional surface-exposed lipoprotein in B12 uptake loci. BtuJ1 binds vitamin B12 and cobinamide (an intermediate in B12 biosynthesis) with low nM affinity, conferring a fitness advantage in B12-limited environments. Regardless of B12 availability, BtuJ1 is the most abundant of the B12-transport components encoded by B. theta. Under B12-replete conditions, BtuJ1 binds the vitamin, generating a readily available pool for transfer to the core BtuBG transport systems during periods of B12 depletion as demonstrated by in vitro and in vivo B12 transfer experiments. Together, these findings expand the known functionalities of the diverse accessory OM proteins employed by Bacteroidota and underscore the sophisticated strategies these human gut commensals use to secure vitamin B12 in the competitive environment of the human gut.
Author(s): Abellon-Ruiz J, Pacheco-Gomez R, Watts J, Hart A, Hirt RP, Basle A, van den Berg B
Publication type: Article
Publication status: Published
Journal: Journal of Molecular Biology
Year: 2026
Volume: 438
Issue: 11
Print publication date: 01/06/2026
Online publication date: 12/03/2026
Acceptance date: 06/03/2026
Date deposited: 14/04/2026
ISSN (print): 0022-2836
ISSN (electronic): 1089-8638
Publisher: Academic Press
URL: https://doi.org/10.1016/j.jmb.2026.169754
DOI: 10.1016/j.jmb.2026.169754
Data Access Statement: The data supporting the findings of this study are available from the corresponding authors upon reasonable request. For X-ray structures, coordinates and structure factors have been deposited in the Protein Data Bank with accession codes 9QPM for Btuj1-CNCbl and 9QPN for Btuj1-CNCbi.
PubMed id: 41831674
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