A conserved TLR5 binding and activation hot spot on flagellin

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473530.do
DOI
10.1038/srep40878
Title
A conserved TLR5 binding and activation hot spot on flagellin
Description
This research was supported by a grant from the Korea Health TechnologyR&D Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea(HI14C1824 to SIY).
abstract
Flagellin is a bacterial protein that polymerizes into the flagellar filament and is essential for bacterial motility. When flagellated bacteria invade the host, flagellin is recognized by Toll-like receptor 5 (TLR5) as a pathogen invasion signal and eventually evokes the innate immune response. Here, we provide a conserved structural mechanism by which flagellins from Gram-negative gamma-proteobacteria and Gram-positive Firmicutes bacteria bind and activate TLR5. The comparative structural analysis using our crystal structure of a complex between Bacillus subtilis flagellin (bsflagellin) and TLR5 at 2.1 angstrom resolution, combined with the alanine scanning analysis of the binding interface, reveals a common hot spot in flagellin for TLR5 activation. An arginine residue (bsflagellin R89) of the flagellin D1 domain and its adjacent residues (bsflagellin E114 and L93) constitute a hot spot that provides shape and chemical complementarity to a cavity generated by the loop of leucine-rich repeat 9 in TLR5. In addition to the flagellin D1 domain, the D0 domain also contributes to TLR5 activity through structurally dispersed regions, but not a single focal area. These results establish the groundwork for the future design of flagellin-based therapeutics.
provenance
Made available in Cube on 2018-09-28T10:22:06Z (GMT). No. of bitstreams: 0
language
English
author
Song, Wan Seok
Jeon, Ye Ji
Namgung, Byeol
Hong, Minsun
Yoon, Sung-il
accessioned
2018-09-28T10:22:06Z
available
2018-09-28T10:22:06Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473530.do
Funder
보건복지부
Funding Program
질환극복기술개발
Project ID
1465021852
Jurisdiction
Rep.of Korea
Project Name
Mechanistic study on innate immune evasion of Helicobacter pylori flagellin and vaccine development
rights
openAccess
type
article


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