title: Leucine-rich repeats and pathogen recognition in Toll-like receptors.
abstract: Toll-like receptors (TLRs) are the major cell-surface initiators of inflammatory responses to pathogens. They bind a wide variety of pathogenic substances through their ectodomains (ECDs). Here, we ask: what is the structural basis for this interaction? Toll-like receptor ECDs comprise 19-25 tandem copies of a motif known as the leucine-rich repeat (LRR). No X-ray structure of a TLR-ECD is currently available but there are several high-resolution LRR-containing proteins that can be used to model TLRs. We suggest that the basic framework of TLRs is a horseshoe-shaped solenoid that contains an extensive beta-sheet on its concave surface, and numerous ligand-binding insertions. Together, these insertions and the beta-sheet could provide a binding surface that is 10-fold greater in area than binding surfaces in antibodies and T-cell receptors.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Building 5, Room 338, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Bell
authors.forename: Gregory E D
authors.initials: GE
authors.lastname: Mullen
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Leifer
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mazzoni
authors.forename: David R
authors.initials: DR
authors.lastname: Davies
authors.forename: David M
authors.initials: DM
authors.lastname: Segal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007111:Immunity, Cellular; D007930:Leucine; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000276:immunology; D020449:Repetitive Sequences, Amino Acid; D016415:Sequence Alignment; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D007930:Leucine