Crystal structure of the human myeloid cell activating receptor TREM-1.
Triggering receptors expressed on myeloid cells (TREM) are a family of recently discovered receptors that play important roles in innate immune responses, such as to activate inflammatory responses and to contribute to septic shock in response to microbial-mediated infections. To date, two TREM receptors in human and several homologs in mice have been identified. We report the 2.6 A resolution crystal structure of the extracellular domain of human TREM-1. The overall fold of the receptor resembles that of a V-type immunoglobulin domain with differences primarily located in the N-terminal strand. TREM-1 forms a "head-to-tail" dimer with 4100 A(2) interface area that is partially mediated by a domain swapping between the first strands. This mode of dimer formation is different from the "head-to-head" dimerization that existed in V(H)V(L) domains of antibodies or V domains of T cell receptors. As a result, the dimeric TREM-1 most likely contains two distinct ligand binding sites.
Radaev
Sergei
S
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Kattah
Michael
M
Rostro
Bertha
B
Colonna
Marco
M
Sun
Peter D
PD
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012984:Software; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1