Disease relevance of PGRP-LC

• Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria [1].
• Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo [1].
• Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections [2].
• PGRP-LC and -LE recognize diaminopimelic acid (DAP)-containing peptidoglycans, which are cell wall components of many gram-negative bacteria and some gram-positive bacteria, and activate the imd pathway to produce antibacterial peptides [3].
• Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E. coli), but not Gram-positive, bacterial infection [1].

High impact information on PGRP-LC

• By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene [2].
• This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria [1].
• Recognition of monomeric and polymeric peptidoglycan required different PGRP-LC splice isoforms, while lipid A recognition required an unidentified soluble factor in the hemolymph of Bombyx morii [4].
• Instead, PGRP-LC and PGRP-LE signaled through a receptor-interacting protein homotypic interaction motif-like motif [5].
• The PGRP-LC cytoplasmic domain is also essential for the formation of dimers, and results suggest that dimerization may be required for receptor activation [6].

Biological context of PGRP-LC

• Three transcripts are generated by alternative splicing of the complex PGRP-LC gene [7].
• Functional diversity of the Drosophila PGRP-LC gene cluster in the response to lipopolysaccharide and peptidoglycan [7].
• Using RNA interference in Drosophila mbn-2 cells, we found that PGRP-LCx is the only isoform required to mediate signals from Gram-positive bacteria and purified bacterial peptidoglycan [7].

Anatomical context of PGRP-LC

• In this study, we have further analyzed the specific PG molecular requirements for Imd activation through the pattern recognition receptor PGRP-LC in both cultured cell line and in flies [8].

Physical interactions of PGRP-LC

• 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 [9].

Other interactions of PGRP-LC

• PGRP-LCx, the default peptidoglycan receptor of the Imd/Relish pathway, has strong affinity for all polymeric peptidoglycans tested and for monomeric peptidoglycan [10].
• The crystal structure at 2.1 angstrom resolution of TCT in complex with the ectodomains of PGRP-LCa and PGRP-LCx shows that TCT is bound to and presented by the LCx ectodomain for recognition by the LCa ectodomain; the latter lacks a canonical peptidoglycan-docking groove conserved in other PGRPs [11].

References