Cited by 540Bacterial Genetics and BiotechnologyDrug Transport and Resistance MechanismsEnzyme Structure and Function

Transmembrane Signaling across the Ligand-Gated FhuA Receptor

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Locher, Kaspar P, Rees, Bernard, Koebnik, Ralf, Mitschler, André, Moulinier, Luc, Rosenbusch, Jurg P, Moras, Dino·1998·Cell

Abstract

FhuA protein facilitates ligand-gated transport of ferrichrome-bound iron across Escherichia coli outer membranes. X-ray analysis at 2.7 A resolution reveals two distinct conformations in the presence and absence of ferrichrome. The monomeric protein consists of a hollow, 22-stranded, antiparallel beta barrel (residues 160-714), which is obstructed by a plug (residues 19-159). The binding site of ferrichrome, an aromatic pocket near the cell surface, undergoes minor changes upon association with the ligand. These are propagated and amplified across the plug, eventually resulting in substantially different protein conformations at the periplasmic face. Our findings reveal the mechanism of signal transmission and suggest how the energy-transducing TonB complex senses ligand binding.

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Crossref · 10.1016/s0092-8674(00)81700-6

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  • Given their overall structural and sequence commonalities, other LGPs likely internalize metal complexes, including Trojan horse antibiotics, by the same or similar mechanisms.

    “Given their overall structural ( Ferguson et al., 1998 ; Locher et al., 1998 ; Buchanan et al., 1999 ; Ferguson et al., 2002 ; Chimento et al., 2003 ; Cobessi et al., 2005a , b ; Buchanan et al., 2007 ; Cobessi et al., 2010 ; Grinter and Lithgow, 2019a , b ; Grinter and Lithgow, 2020 ) and sequence ( Klebba et al., 2021 ) commonalities, other LGPs likely internalize metal complexes, including Troj”

    From Specificity and mechanism of TonB-dependent ferric catecholate uptake by Fiu (2024) · cites this paper as Locher et al., 1998

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Authors
Locher, K. P., Rees, B., Koebnik, R., Mitschler, A., Moulinier, L., Rosenbusch, J. P., & Moras, D.
Affiliations
  • University of Basel (CH)
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
Moras, Dino
Venue
Cell
Publisher
Elsevier BV
Published
1998-12
Volume
95
Issue
6
Pages
771-778
ISSN
0092-8674 (ISSN-L)
OpenAlex
W163411833
Cited by
540
References
48
Citations by year
2026: 8 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 11 · 2019: 9 · 2018: 14 · 2017: 16 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 16 · 2012: 23
FWCI
18.83
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
ferrichrome, transmembrane signaling, Escherichia coli outer membrane, beta-barrel proteins, protein conformational change, ligand binding, signal transduction
MeSH terms
Allosteric Regulation, Amino Acid Sequence, Bacterial Outer Membrane Proteins, Cell Membrane, Ferrichrome, Ligands, Molecular Sequence Data, Protein Conformation, Receptors, Virus, Signal Transduction, Crystallography, X-Ray, Escherichia coli Proteins

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