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primary topic: A communication network within the cytoplasmic domain of toll-like receptors has remained conserved during evolution.

A communication network within the cytoplasmic domain of toll-like receptors has remained conserved during evolution.
type: AcademicArticle
type: Article
abstract: Toll/IL-1R (TIR) domain, that is, the cytoplasmic domain, in toll-like receptors (TLRs) from different species showed high sequence conservation in stretches spread across the surface as well as the core of the domain. To probe the structure-function significance of these residues, especially those coming from the core of TIR domains, we analyzed molecular dynamics trajectories of sequence similarity based models of human TIR domains. This study brought forth that N-terminal of the TIR domain simultaneously interacts with the flanking residues of the BB loop and central β-sheets. At the same time, residues of the central β-strands form favorable contacts with the DD loop and C-terminal, thus forming a two-way circuit between the N- and C-termini. In this work, the array of intradomain interactions is termed as communication network. Importantly, the "hubs" of this communication network were found to be conserved in all human TLRs. Earlier mutagenesis-function correlation work brought forth that certain mutations in the "core" of the TIR domain of TLR4 (e.g. in IFI767-769AAA and L815A) led to almost complete abrogation of signaling and reasoning for this dramatic loss-of-function has remained unclear, since these sites are not surface exposed. Using MD studies, we show here that this communication network gets disrupted in mutants of human TLR4 which were earlier reported to be functionally compromised. Extension of MD studies to heterodimer of TLR1/2 suggested that this evolutionarily conserved communication network senses the interactions formed upon dimerization and relays it to surfaces which are not involved in direct interdomain contacts.
date: 2014
volume: 32
issue: 5
is part of: Journal of biomolecular structure & dynamics
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

Taylor & Francis
type: Organization

Journal of biomolecular structure & dynamics
type: Collection
issn: 15380254

Ashish Ganguly
type: Person
given name: Ashish
family name: Ganguly

U Bharat K Pattnaik
type: Person
given name: U Bharat K
family name: Pattnaik

Shikha Singh
type: Person
given name: Shikha
family name: Singh

Amin Sagar
type: Person
given name: Amin
family name: Sagar

Yogendra S Rathore
type: Person
given name: Yogendra S
family name: Rathore

Kalpana Pandey
type: Person
given name: Kalpana
family name: Pandey

HTML Summary of #1695 A communication network within the cytoplasmic domain of toll-like receptors has remained conserved during evolution.
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primary topic: A communication network within the cytoplasmic domain of toll-like receptors has remained conserved during evolution.

QR Microbiology
type: Concept