Effect of C-Terminus Modification in Salmonella typhimurium FliC on Protein Purification Efficacy and Bioactivity

Khani, Mohammad-Hosein; Bagheri, Masoumeh; Dehghanian, Ali; Zahmatkesh, Azadeh; Bidhendi, Soheila Moradi; Salehi-Najafabadi, Zahra; Banihashemi, Reza

doi:10.1007/s12033-018-0135-y

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…TLR5 activation requires the formation of a symmetric 2:2 flagellin:TLR5 complex (9,24). How this complex is assembled remains unclear, although it is widely stated that flagellin binding induces TLR5 dimerization (19,(25)(26)(27). Early cryo-electron microscopy work revealed, however, that human TLR5 forms asymmetric homodimers in the absence of flagellin, a conformation likely associated with multiple ligand binding sites and thus a possible target of the FliC D0 domain (28).…”

Section: D0 Binding Site Targeted Flagellin To Preformed Tlr5 Dimersmentioning

confidence: 99%

Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

et al. 2023

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Flagellin, the protein subunit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor 5 (TLR5) after pattern recognition or evades TLR5 through lack of recognition. This binary response fails to explain the weak agonism of flagellins from commensal bacteria, raising the question of how TLR5 response is tuned. Here, we screened abundant flagellins present in metagenomes from human gut for both TLR5 recognition and activation and uncovered a class of flagellin-TLR5 interaction termed silent recognition. Silent flagellins were weak TLR5 agonists despite pattern recognition. Receptor activity was tuned by a TLR5-flagellin interaction distal to the site of pattern recognition that was present in Salmonella flagellin but absent in silent flagellins. This interaction enabled flagellin binding to preformed TLR5 dimers and increased TLR5 signaling by several orders of magnitude. Silent recognition by TLR5 occurred in human organoids and mice, and silent flagellin proteins were present in human stool. These flagellins were produced primarily by the abundant gut bacteria Lachnospiraceae and were enriched in nonindustrialized populations. Our findings provide a mechanism for the innate immune system to tolerate commensal-derived flagellins while remaining vigilant to the presence of flagellins produced by pathogens.

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Section: D0 Binding Site Targeted Flagellin To Preformed Tlr5 Dimersmentioning

confidence: 99%

Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

et al. 2023

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show abstract

“…TLR5 activation requires the formation of a symmetric 2:2 flagellin:TLR5 complex (9,22). How this complex is assembled remains unclear, although it is widely stated that flagellin binding induces TLR5 dimerization (11,(23)(24)(25). Early cryo-EM work revealed, however, that human TLR5 forms asymmetric homodimers in the absence of flagellin, a conformation likely associated with multiple ligand binding sites, and thus a possible target of the FliC D0 domain (26).…”

Section: Main Textmentioning

confidence: 99%

Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

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Lee

et al. 2022

Preprint

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Flagellin, the protein unit of the bacterial flagellum, stimulates the innate immune receptor Toll-like receptor (TLR)5 following pattern recognition, or evades TLR5 through lack of recognition. This binary response fails to explain the weak agonism of flagellins from commensal bacteria, raising the question of how TLR5 response is tuned. Here, we describe a novel class of flagellin-TLR5 interaction, termed silent recognition. Silent flagellins are weak agonists despite high affinity binding to TLR5. This dynamic response is tuned by TLR5-flagellin interaction distal to the site of pattern recognition. Silent flagellins are produced primarily by the abundant gut bacteria Lachnospiraceae and are enriched in non-Western populations. These findings provide a mechanism for the innate immune system to tolerate commensal-derived flagellins.

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Soluble overexpression of a flagellin derivative from Salmonella enterica using synonymous codon substitutions of 5′-coding region in Escherichia coli

et al. 2019

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Effect of C-Terminus Modification in Salmonella typhimurium FliC on Protein Purification Efficacy and Bioactivity

Cited by 7 publications

References 28 publications

Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

Silent recognition of flagellins from human gut commensal bacteria by Toll-like receptor 5

Soluble overexpression of a flagellin derivative from Salmonella enterica using synonymous codon substitutions of 5′-coding region in Escherichia coli

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