A scavenger function for a Drosophila peptidoglycan recognition protein.
Recent studies of peptidoglycan recognition protein (PGRP) have shown that 2 of the 13 Drosophila PGRP genes encode proteins that function as receptors mediating immune responses to bacteria. We show here that another member, PGRP-SC1B, has a totally different function because it has enzymatic activity and thereby can degrade peptidoglycan. A mass spectrometric analysis of the cleavage products demonstrates that the enzyme hydrolyzes the lactylamide bond between the glycan strand and the cross-linking peptides. This result assigns the protein as an N-acetylmuramoyl-l-alanine amidase (EC ), and the corresponding gene is thus the first of this class to be described from a eukaryotic organism. Mutant forms of PGRP-SC1B lacking a potential zinc ligand are enzymatically inactive but retain their peptidoglycan affinity. The immunostimulatory properties of PGRP-SC1B-degraded peptidoglycan are much reduced. This is in striking contrast to lysozyme-digested peptidoglycan, which retains most of its elicitor activity. This points toward a scavenger function for PGRP-SC1B. Furthermore, a sequence homology comparison with phage T7 lysozyme, also an N-acetylmuramoyl-l-alanine amidase, shows that as many as six of the Drosophila PGRPs could belong to this class of proteins.
Mellroth
Peter
P
Department of Microbiology, Stockholm University, S-106 91 Stockholm, Sweden.
Karlsson
Jenny
J
Steiner
Hakan
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001665:Binding Sites; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D006868:Hydrolysis; D007313:Insecta; D007700:Kinetics; D008024:Ligands; D013058:Mass Spectrometry; D009113:Muramidase / Q000378:metabolism; D009154:Mutation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010457:Peptidoglycan / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors; D015032:Zinc / Q000737:chemistry
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D008024:Ligands; D010455:Peptides; D010457:Peptidoglycan; D011994:Recombinant Proteins; C118897:peptidoglycan recognition protein; D012313:RNA; D009113:Muramidase; D009238:N-Acetylmuramoyl-L-alanine Amidase; D015032:Zinc