2cb3
From Proteopedia
Crystal structure of peptidoglycan recognition protein-LE in complex with tracheal cytotoxin (monomeric diaminopimelic acid-type peptidoglycan)
Structural highlights
FunctionPGPLE_DROME Peptidoglycan-recognition protein that plays a key role in innate immunity by binding to murein peptidoglycans (PGN) of Gram-negative bacteria and activating the imd/Relish pathway. Has no activity against on Gram-positive bacteria. Binds to diaminopimelic acid-type PGN (DAP-type PGN), an activator of the imd/Relish pathway. Functions synergistically with PGRP-LC in producing resistance to E.coli and B.megaterium infections, which have the DAP-type peptidoglycan. Acts both upstream and in parallel with PGRP-LC in the imd/Relish pathway, and is required for infection-dependent activation of melanization. Required for Relish processing and nuclear translocation following proteolytic cleavage. Its localization suggests a role in the recognition and subsequent activation of the signaling at the first point of contact with invading bacteria.[1] [2] 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 PubMedDrosophila peptidoglycan recognition protein (PGRP)-LCx and -LCa are receptors that preferentially recognize meso-diaminopimelic acid (DAP)-type peptidoglycan (PGN) present in Gram-negative bacteria over lysine-type PGN of gram-positive bacteria and initiate the IMD signaling pathway, whereas PGRP-LE plays a synergistic role in this process of innate immune defense. How these receptors can distinguish the two types of PGN remains unclear. Here the structure of the PGRP domain of Drosophila PGRP-LE in complex with tracheal cytotoxin (TCT), the monomeric DAP-type PGN, reveals a buried ionic interaction between the unique carboxyl group of DAP and a previously unrecognized arginine residue. This arginine is conserved in the known DAP-type PGN-interacting PGRPs and contributes significantly to the affinity of the protein for the ligand. Unexpectedly, TCT induces infinite head-to-tail dimerization of PGRP-LE, in which the disaccharide moiety, but not the peptide stem, of TCT is positioned at the dimer interface. A sequence comparison suggests that TCT induces heterodimerization of the ectodomains of PGRP-LCx and -LCa in a closely analogous manner to prime the IMD signaling pathway, except that the heterodimer formation is nonperpetuating. Structural basis for preferential recognition of diaminopimelic acid-type peptidoglycan by a subset of peptidoglycan recognition proteins.,Lim JH, Kim MS, Kim HE, Yano T, Oshima Y, Aggarwal K, Goldman WE, Silverman N, Kurata S, Oh BH J Biol Chem. 2006 Mar 24;281(12):8286-95. Epub 2006 Jan 20. PMID:16428381[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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