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Crystal structure of drosophila peptidoglycan recognition protein SD (PGRP-SD)Crystal structure of drosophila peptidoglycan recognition protein SD (PGRP-SD)
Structural highlights
FunctionPGPSD_DROME Peptidoglycan-recognition protein that plays a key role in innate immnunity by binding to peptidoglycans (PGN) of Gram-positive bacteria and activating the Toll pathway. Has no activity against on Gram-negative bacteria and fungi. Shows some partial redundancy with PRPGP-SA in Gram-positive bacteria recognition. May act by activating the proteolytic cleavage of Spatzle and the subsequent activation of Toll pathway. Recognizes S.aureus PGN.[1] 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 PubMedIn Drosophila the synthesis of antimicrobial peptides in response to microbial infections is under the control of the Toll and immune deficiency (Imd) signaling pathways. The Toll signaling pathway responds mainly to Gram-positive bacterial and fungal infection while the Imd pathway mediates the response to Gram-negative bacteria. Microbial recognition upstream of Toll involves, at least in part, peptidoglycan recognition proteins (PGRPs). The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and Gram-negative binding protein 1 (GNBP1) that cooperate to detect the presence of lysine-type peptidoglycan in the host. Recently it has been shown that a loss-of-function mutation in peptidoglycan recognition protein SD (PGRP-SD) severely exacerbates the PGRP-SA and GNBP1 mutant phenotypes. Here we have solved the crystal structure of PGRP-SD at 1.5A resolution. Comparison with available structures of PGRPs in complex with their peptidoglycan (PGN) ligand strongly suggests a diaminopimelic acid (DAP) specificity for PGRP-SD. This result is supported by pull-down assays with insoluble PGNs. In addition we show that Toll pathway activation after infection by DAP-type PGN containing bacteria is clearly reduced in PGRP-SD mutant flies. Our hypothesis is that the role of PGRP-SD is the recognition of DAP-type PGNs responsible for the activation of the Toll pathway by Gram-negative bacteria. Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan.,Leone P, Bischoff V, Kellenberger C, Hetru C, Royet J, Roussel A Mol Immunol. 2008 May;45(9):2521-30. Epub 2008 Mar 4. PMID:18304640[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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