Siderophore-Mediated Iron Transport: Crystal Structure of FhuA with Bound Lipopolysaccharide

TLDR

FhuA is an outer membrane receptor for ferrichrome‑iron in *E. coli* that, together with TonB, mediates active transport of ferric siderophores across Gram‑negative bacterial membranes. The study proposes a structural mechanism for TonB‑dependent siderophore transport based on sequence homology and mutagenesis data. FhuA is a 22‑strand β‑barrel with a distinct cork domain of a four‑strand β sheet and four α helices, and ligand binding induces conformational changes that signal the receptor’s loaded state to the periplasmic pocket.

Abstract

FhuA, the receptor for ferrichrome-iron in Escherichia coli , is a member of a family of integral outer membrane proteins, which, together with the energy-transducing protein TonB, mediate the active transport of ferric siderophores across the outer membrane of Gram-negative bacteria. The three-dimensional structure of FhuA is presented here in two conformations: with and without ferrichrome-iron at resolutions of 2.7 and 2.5 angstroms, respectively. FhuA is a β barrel composed of 22 antiparallel β strands. In contrast to the typical trimeric arrangement found in porins, FhuA is monomeric. Located within the β barrel is a structurally distinct domain, the “cork,” which mainly consists of a four-stranded β sheet and four short α helices. A single lipopolysaccharide molecule is noncovalently associated with the membrane-embedded region of the protein. Upon binding of ferrichrome-iron, conformational changes are transduced to the periplasmic pocket of FhuA, signaling the ligand-loaded status of the receptor. Sequence homologies and mutagenesis data are used to propose a structural mechanism for TonB-dependent siderophore-mediated transport across the outer membrane.