Disease relevance of ECs0154

• FhuA protein facilitates ligand-gated transport of ferrichrome-bound iron across Escherichia coli outer membranes [1].
• FhuA, a transporter of the Escherichia coli outer membrane, is converted into a channel upon binding of bacteriophage T5 [2].
• FhuA, the ferrichrome OMT in Escherichia coli, and FptA, the pyochelin (Pch) OMT in Pseudomonas aeruginosa, were both able to bind in vitro and in vivo the apo-forms and the ferric forms of their corresponding siderophore at a common binding site [3].
• In Escherichia coli, the mere interaction of the phage T5 with its outer membrane receptor, the ferrichrome transporter FhuA, is sufficient to trigger the release of the DNA from the phage capsid [4].
• FcuA shared 34.6% amino acid sequence homology with FatA, the anguibactin receptor of Vibrio anguillarum, but only 20.6% homology with FhuA, the ferrichrome receptor of E. coli [5].

High impact information on ECs0154

• Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes [1].
• Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide [6].
• These data suggest that binding of T5 to loop 322-355 of FhuA, which constitutes the T5 binding site, unmasks an inner channel in FhuA [2].
• The transport-active conformation of FhuA is mediated by a TonB-induced conformational change in response to the energized cytoplasmic membrane [7].
• When T5 phage binds to its membrane protein receptor, FhuA, its double stranded DNA (120,000 bp) is progressively released base pair after base pair in the surrounding medium [8].

Chemical compound and disease context of ECs0154

• FhuADelta5-160 conferred sensitivity to the phages and colicin M at levels similar to that of wild-type FhuA, and to albomycin and rifamycin CGP 4832 [9].
• The Escherichia coli outer membrane ferrichrome transporter FhuA was purified chromatographically in a neutral detergent (octyl glucoside or dodecyl maltoside) [10].
• Each insertion spliced a 13-amino-acid antigenic determinant (the C3 epitope of poliovirus) at a different position within FhuA [11].
• The Fct protein has 36% sequence homology with the E. coli ferrichrome receptor FhuA and the Yersinia enterocolitica ferrioxamine receptor FoxA [12].
• Deletion of the proline-rich region of TonB disrupts formation of a 2:1 complex with FhuA, an outer membrane receptor of Escherichia coli [13].

Biological context of ECs0154

• Since the loop extending from residue 316 to 356 is part of the active site of FhuA, it probably controls the permeability of the channel [7].
• FhuA-mediated phage genome transfer into liposomes: a cryo-electron tomography study [4].
• Dimerization of TonB is not essential for its binding to the outer membrane siderophore receptor FhuA of Escherichia coli [14].
• FoxA shared 33% amino acid sequence homology with FhuA, the ferrichrome receptor of Escherichia coli [15].
• The ferrichrome receptors FcuA from Y. enterocolitica and FhuA from E. coli had slightly different substrate specificities [5].

Anatomical context of ECs0154

• During siderophore transport into the periplasm, the FhuA cork domain has been proposed to undergo conformational changes that allow transport through the barrel lumen; alternatively, the cork may be completely displaced from the barrel [16].

Associations of ECs0154 with chemical compounds

• These results indicate that, in vivo, the binding of ferricrocin to FhuA enhances complex formation between the receptor and TonB [17].
• We exchanged and deleted the N termini of two such siderophore receptors, FepA and FhuA, which recognize and transport ferric enterobactin and ferrichrome, respectively [18].
• Conversely, a monoclonal antibody that binds near the N terminus of FhuA reduced the retention of TonB by histidine-tagged FhuA [17].
• Results from trypsin digestion were interpreted as a conformational change in FhuA which had occurred upon ferrichrome binding, thereby preventing access of trypsin to lysine 67 [19].
• Analyses of these sequences using the Receptor Ligand Contacts (RELIC) suite of programs revealed clusters of multiply aligned peptides that mapped to FhuA [20].

Analytical, diagnostic and therapeutic context of ECs0154

• Using cryoelectron microscopy, we have visualized the structures formed after T5 phage DNA is released into neutral unilamellar proteoliposomes reconstituted with the receptor FhuA [8].
• Subsequent SDS-PAGE analysis revealed two distinct species: FhuA containing a disulfide bond and FhuA with free sulfhydryl groups [16].
• Direct interaction of pb5 with FhuA was demonstrated by isolating a pb5/FhuA complex using size-exclusion chromatography [21].
• SDS-PAGE and differential scanning calorimetry experiments highlighted the great stability of the complex: (i) it was not dissociated by 2% SDS even when the temperature was raised to 70 degrees C; (ii) thermal denaturation of the complex occurred at 85 degrees C, while pb5 and FhuA were denatured at 45 degrees C and 74 degrees C, respectively [21].
• Isothermal titration calorimetry measurements demonstrate that TonB-CTD interacts with the FhuA-derived peptide with a K(D)=36(+/-7) microM [22].

References