1z6i
Crystal structure of the ectodomain of Drosophila transmembrane receptor PGRP-LCa
Structural highlights
FunctionPGPLC_DROME Major activator of the imd/Relish pathway and is likely to encode a pattern recognition molecule for the humoral immune response. Required for Relish processing and nuclear translocation following proteolytic cleavage. Involved in the response to lipopolysaccharide (LPS) and peptidoglycan of Gram-negative bacteria. The different isoforms probably display different recognition capabilities to various microbial patterns. Isoform a and isoform x mediate the induction by LPS and Gram-negative bacteria, while isoform x mediates the induction by peptidoglycan.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structure of the ectodomain of Drosophila peptidoglycan-recognition protein LCa suggests a molecular mechanism for pattern recognition.,Chang CI, Ihara K, Chelliah Y, Mengin-Lecreulx D, Wakatsuki S, Deisenhofer J Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10279-84. Epub 2005 Jul 8. PMID:16006509[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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