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Article
Nature Immunology  4, 1247 - 1253 (2003)
Published online: 16 November 2003; | doi:10.1038/ni1011


There is a Corrigendum (April 2004) associated with this Article.

Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility

Kelly D Smith1, 2, Erica Andersen-Nissen1, 3, Fumitaka Hayashi1, 3, 6, Katie Strobe1, Molly A Bergman4, Sara L Rassoulian Barrett4, Brad T Cookson4, 5 & Alan Aderem1

1  Institute for Systems Biology, 1441 North 34th Street, Seattle, Washington 98103, USA.

2  Department of Pathology, the University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.

3  Department of Immunology, the University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.

4  Department of Microbiology, the University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.

5  Department of Laboratory Medicine, the University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.

6  Present address: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129−2020, USA.

Correspondence should be addressed to Kelly D Smith kelsmith@u.washington.edu
Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and activates host inflammatory responses. In this study, we examine the nature of the TLR5-flagellin interaction. With deletional, insertional and alanine-scanning mutagenesis, we precisely mapped the TLR5 recognition site on flagellin to a cluster of 13 amino acid residues that participate in intermolecular interactions within flagellar protofilaments and that are required for bacterial motility. The recognition site is buried in the flagellar filament, and monomeric flagellin, but not the filamentous molecule, stimulated TLR5. Finally, flagellin coprecipitated with TLR5, indicating close physical interaction between the molecules. These studies demonstrate the exquisite ability of the innate immune system to precisely target a conserved site on flagellin that is essential for bacterial motility.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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