A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin

A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin

The molecular basis for Toll-like receptor (TLR) recognition of microbial ligands is unknown. We demonstrate that mouse and human TLR5 discriminate between different flagellins, and we use this difference to map the flagellin recognition site on TLR5 to 228 amino acids of the extracellular domain. T...

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Main Authors: Andersen-Nissen, Erica, Smith, Kelly D., Bonneau, Richard, Strong, Roland K., Aderem, Alan
Format: Online
Language:English
Published: The Rockefeller University Press 2007
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118731/
id pubmed-2118731
recordtype oai_dc
spelling pubmed-21187312007-12-13 A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin Andersen-Nissen, Erica Smith, Kelly D. Bonneau, Richard Strong, Roland K. Aderem, Alan Articles The molecular basis for Toll-like receptor (TLR) recognition of microbial ligands is unknown. We demonstrate that mouse and human TLR5 discriminate between different flagellins, and we use this difference to map the flagellin recognition site on TLR5 to 228 amino acids of the extracellular domain. Through molecular modeling of the TLR5 ectodomain, we identify two conserved surface-exposed regions. Mutagenesis studies demonstrate that naturally occurring amino acid variation in TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. Mutations within one conserved surface identify residues D295 and D367 as important for flagellin recognition. These studies localize flagellin recognition to a conserved surface on the modeled TLR5 structure, providing detailed analysis of the interaction of a TLR with its ligand. These findings suggest that ligand binding at the β sheets results in TLR activation and provide a new framework for understanding TLR–agonist interactions. The Rockefeller University Press 2007-02-19 /pmc/articles/PMC2118731/ /pubmed/17283206 http://dx.doi.org/10.1084/jem.20061400 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Andersen-Nissen, Erica
Smith, Kelly D.
Bonneau, Richard
Strong, Roland K.
Aderem, Alan
spellingShingle Andersen-Nissen, Erica
Smith, Kelly D.
Bonneau, Richard
Strong, Roland K.
Aderem, Alan
A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
author_facet Andersen-Nissen, Erica
Smith, Kelly D.
Bonneau, Richard
Strong, Roland K.
Aderem, Alan
author_sort Andersen-Nissen, Erica
title A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
title_short A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
title_full A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
title_fullStr A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
title_full_unstemmed A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin
title_sort conserved surface on toll-like receptor 5 recognizes bacterial flagellin
description The molecular basis for Toll-like receptor (TLR) recognition of microbial ligands is unknown. We demonstrate that mouse and human TLR5 discriminate between different flagellins, and we use this difference to map the flagellin recognition site on TLR5 to 228 amino acids of the extracellular domain. Through molecular modeling of the TLR5 ectodomain, we identify two conserved surface-exposed regions. Mutagenesis studies demonstrate that naturally occurring amino acid variation in TLR5 residue 268 is responsible for human and mouse discrimination between flagellin molecules. Mutations within one conserved surface identify residues D295 and D367 as important for flagellin recognition. These studies localize flagellin recognition to a conserved surface on the modeled TLR5 structure, providing detailed analysis of the interaction of a TLR with its ligand. These findings suggest that ligand binding at the β sheets results in TLR activation and provide a new framework for understanding TLR–agonist interactions.
publisher The Rockefeller University Press
publishDate 2007
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118731/
_version_ 1611414933772173312

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