Abstract

The NOD-like receptors (NLRs) and Toll-like receptors (TLRs) are pattern recognition receptors that are involved in the innate, pathogen pattern recognition system. The TLR and NLR receptors contain leucine-rich repeats (LRRs) that are responsible for ligand interactions. In LRRs short β-strands stack parallel and then the LRRs form a super helical arrangement of repeating structural units (called a coil of solenoids). The structures of the LRR domains of NLRC4, NLRP1, and NLRX1 in NLRs and of TLR1-5, TLR6, TLR8, TLR9 in TLRs have been determined. Here we report nine geometrical parameters that characterize the LRR domains; these include four helical parameters from HELFIT analysis. These nine parameters characterize well the LRR structures in NLRs and TLRs; the LRRs of NLR adopts a right-handed helix. In contrast, the TLR LRRs adopt either a left-handed helix or are nearly flat; RP105 and CD14 also adopt a left-handed helix. This geometrical analysis subdivides TLRs into four groups consisting of TLR3/TLR8/TLR9, TLR1/TLR2/TRR6, TLR4, and TLR5; these correspond to the phylogenetic tree based on amino acid sequences. In the TLRs an ascending lateral surface that consists of loops connecting the β-strand at the C-terminal side is involved in protein, protein/ligand interactions, but not the descending lateral surface on the opposite side.

Highlights

  • Nucleotide binding oligomerization domain (NOD-like) receptors (NLRs) and Toll-like receptors (TLRs) are pattern recognition receptors that together with RIG-I-like receptor and C-type lectin families make up the innate, pathogen pattern recognition system [1,2,3,4,5,6,7,8]

  • The Drosophila Toll receptor as well as NLRC4, NLRP1, and NLRX adopt a right handed helix, while TLR1-5, TLR6, TLR8, and TLR9 adopt either a left handed helix or are nearly flat. This geometrical analysis subdivides TLRs into four groups consisting of TLR3/TLR8/TLR9, TLR1/TLR2/TRR6, TLR4, and TLR5

  • From this review several conclusions emerge about the leucine-rich repeats (LRRs) structures in NOD-like receptors (NLRs) and TLRs

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Summary

Introduction

Nucleotide binding oligomerization domain (NOD-like) receptors (NLRs) and Toll-like receptors (TLRs) are pattern recognition receptors that together with RIG-I-like receptor (retinoic acid inducible gene 1) and C-type lectin families make up the innate, pathogen pattern recognition system [1,2,3,4,5,6,7,8]. We calculated helical parameters of 642 LRRs of known structure from 114 proteins by HELFIT analysis [23]. We focus on NLRs and TLRs and calculate nine geometrical parameters of all of their known LRR structures together with secondary structure analysis of individual LRR units. These nine parameters well characterize the LRR structures in NLRs and TLRs. The Drosophila Toll receptor as well as NLRC4, NLRP1, and NLRX adopt a right handed helix, while TLR1-5, TLR6, TLR8, and TLR9 adopt either a left handed helix or are nearly flat. In the TLRs an ascending lateral surface, but not the descending lateral surface, is involved in protein, protein/ligand interactions

Structural Secondary Structure Analysis of LRRs
Geometrical Analysis
The LRRs in NLRs
Human NLRP1
Human NLRX1
Mouse NLRC4
The LRRs in TLRs
The TLR3—dsRNA Complex
The TLR3—Fab Complex
The TLR8—Complexes with Agonistic Ligands
The TLR8—Complexes with Degradation Products of ssRNA
The TLR9—CpG-DNA Complex
Human and Mouse TLR4
TLR4 Complexes with Antagonistic Ligands
Human and Zebrafish TLR5
TLR5-Flagellin Complex
Human and Mouse CD14
Drosophila Toll Receptor
Conclusions
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