Leucine Rich Repeat protein

Toll-like Receptors contain large LRR domains

Toll-like Receptors dimerize along with another pair of proteins, shown in spacefilling. This complex bind the bacterial lipopolysaccharide (LPS).

The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex.
Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO.
Nature. 2009 Apr 30;458(7242):1191-5.

(PubMed)

3fxi (PDB)

 

The structural biology of Toll-like receptors.
Botos I, Segal DM, Davies DR.
Structure. 2011 Apr 13;19(4):447-59. doi: 10.1016/j.str.2011.02.004. Review.
PMID: 21481769 Free PMC Article

Abstract
The membrane-bound Toll-like receptors (TLRs) trigger innate immune responses after recognition of a wide variety of pathogen-derived compounds. Despite the wide range of ligands recognized by TLRs, the receptors share a common structural framework in their extracellular, ligand-binding domains. These domains all adopt horseshoe-shaped structures built from leucine-rich repeat motifs. Typically, on ligand binding, two extracellular domains form an "m"-shaped dimer sandwiching the ligand molecule bringing the transmembrane and cytoplasmic domains in close proximity and triggering a downstream signaling cascade. Although the ligand-induced dimerization of these receptors has many common features, the nature of the interactions of the TLR extracellular domains with their ligands varies markedly between TLR paralogs.

The leucine-rich repeat structure.
Bella J, Hindle KL, McEwan PA, Lovell SC.
Cell Mol Life Sci. 2008 Aug;65(15):2307-33.

Abstract
The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.