title: Crystal structure of human triggering receptor expressed on myeloid cells 1 (TREM-1) at 1.47 A.
abstract: The triggering receptor expressed on myeloid cells (TREM) family of single extracellular immunoglobulin receptors includes both activating and inhibitory isoforms whose ligands are unknown. TREM-1 activation amplifies the Toll-like receptor initiated responses to invading pathogens allowing the secretion of pro-inflammatory chemokines and cytokines. Hence, TREM-1 amplifies the inflammation induced by both bacteria and fungi, and thus represents a potential therapeutic target. We report the crystal structure of the human TREM-1 extracellular domain at 1.47 A resolution. The overall fold places it within the V-type immunoglobulin domain family and reveals close homology with Ig domains from antibodies, T-cell receptors and other activating receptors, such as NKp44. With the additional use of analytical ultracentrifugation and 1H NMR spectroscopy of both human and mouse TREM-1, we have conclusively demonstrated the monomeric state of this extracellular ectodomain in solution and, presumably, of the TREM family in general.
authors.affiliation: Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Kelker
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Foss
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Peti
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Kelly
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011971:Receptors, Immunologic / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014461:Ultracentrifugation
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1