title: Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition.
abstract: The peptidoglycan-recognition protein LCa (PGRP-LCa) is a transmembrane receptor required for activation of the Drosophila immune deficiency pathway by monomeric Gram-negative peptidoglycan. We have determined the crystal structure of the ectodomain of PGRP-LCa at 2.5-A resolution and found two unique helical insertions in the LCa ectodomain that disrupt an otherwise L-shaped peptidoglycan-docking groove present in all other known PGRP structures. The deficient binding of PGRP-LCa to monomeric peptidoglycan was confirmed by biochemical pull-down assays. Recognition of monomeric peptidoglycan involves both PGRP-LCa and -LCx. We showed that association of the LCa and LCx ectodomains in vitro depends on monomeric peptidoglycan. The presence of a defective peptidoglycan-docking groove, while preserving a unique role in mediating monomeric peptidoglycan induction of immune response, suggests that PGRP-LCa recognizes the exposed structural features of a monomeric muropeptide when the latter is bound to and presented by the ectodomain of PGRP-LCx. Such features include N-acetyl glucosamine and the anhydro bond in the glycan of the muropeptide, which have been demonstrated to be critical for immune stimulatory activity.
authors: Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA.
authors: Chung-I
authors: CI
authors: Chang
authors: Kentaro
authors: K
authors: Ihara
authors: Yogarany
authors: Y
authors: Chelliah
authors: Dominique
authors: D
authors: Mengin-Lecreulx
authors: Soichi
authors: S
authors: Wakatsuki
authors: Johann
authors: J
authors: Deisenhofer
mesh_terms: D000818:Animals; D016367:Baculoviridae; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003001:Cloning, Molecular; D003461:Crystallography; D004330:Drosophila / Q000737:chemistry* / Q000276:immunology; D005822:Genetic Vectors; D008958:Models, Molecular; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding
chemical_list: D002352:Carrier Proteins; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein