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Peptidoglycan Recognition Proteins: Major Regulators of Drosophila Immunity
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

All eukaryotic organisms have an innate immune system characterized by germ-line encoded receptors and effector molecules, which mediate detection and clearance of microbes such as bacteria, fungi, and parasites. VertebrateDrosophila as a genetically tractable organism with a

This thesis concerns the peptidoglycan recognition protein (PGRP) gene family in the fruit fly. The family consists of thirteen genes, of which a few have been reported to be part of the signaling pathways that regulates immune

Data presented show that the putative receptors have affinity for peptidoglycan, but not for lipopolysaccharide, or the fungal cell wall polymer beta-glucan. PGRP-SA, receptor of the Toll pathway, has a preference for

In a search for novel PGRP receptors I found two PGRP proteins that instead displayed enzymatic activity towards peptidoglycan. They are of the N-actylmuramoyl L-alanine amidase type, which degrades peptidoglycan by splittingStaphylococcus aureus peptidoglycan looses its immune elicitor capacity. This is in contrast to lysozyme-degraded peptidoglycan, which isDrosophila PGRPs to be potential enzymes. PGRP-SB1 is the other enzymatic PGRP described within this thesis. It has a moreBacillus megaterium.

In conclusion, receptor PGRP proteins binds bacterial peptidoglycan and triggers immune gene pathways and enzymatic PGRPs have the capacity to reduce the elicitor property of peptidoglycan.

Place, publisher, year, edition, pages
Stockholm: Institutionen för genetik, mikrobiologi och toxikologi , 2005. , 58 p.
Keyword [en]
Innate immunity, peptidoglycan recognition protein, PGRP, Toll, Imd, Drosophila immunity
National Category
Pathobiology
Identifiers
URN: urn:nbn:se:su:diva-646ISBN: 91-7155-105-0 (print)OAI: oai:DiVA.org:su-646DiVA: diva2:196517
Public defence
2005-09-28, De Geersalen, Geovetenskapens hus, Svante Arrhenius väg 8 A, Stockholm, 13:00 (English)
Opponent
Supervisors
Available from: 2005-09-06 Created: 2005-09-06 Last updated: 2010-01-11Bibliographically approved
List of papers
1. A scavenger function for a Drosophila peptidoglycan recognition protein
Open this publication in new window or tab >>A scavenger function for a Drosophila peptidoglycan recognition protein
2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 9, 7059-7064 p.Article in journal (Refereed) Published
Abstract [en]

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 anN-acetylmuramoyl-l-alanine amidase (EC3.5.1.28), 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.

Identifiers
urn:nbn:se:su:diva-20032 (URN)10.1074/jbc.M208900200 (DOI)12496260 (PubMedID)
Available from: 2007-11-21 Created: 2007-11-21 Last updated: 2017-12-13Bibliographically approved
2. PGRP-SB1 - an N-acetylmuramoyl L-alanine amidase with antibacterial activity
Open this publication in new window or tab >>PGRP-SB1 - an N-acetylmuramoyl L-alanine amidase with antibacterial activity
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-24031 (URN)
Note
Part of urn:nbn:se:su:diva-646Available from: 2005-09-06 Created: 2005-09-06 Last updated: 2010-01-13Bibliographically approved
3. Functional Diversity of the Drosophila PGRP-LC Gene Cluster in the Response to Lipopolysaccharide and Peptidoglycan
Open this publication in new window or tab >>Functional Diversity of the Drosophila PGRP-LC Gene Cluster in the Response to Lipopolysaccharide and Peptidoglycan
Show others...
2003 In: J. Biol. Chem., ISSN 0021-9258, Vol. 278, no 29, 26319-26322. p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24032 (URN)
Note
Part of urn:nbn:se:su:diva-646Available from: 2005-09-06 Created: 2005-09-06Bibliographically approved
4. Monomeric and Polymeric Gram-Negative Peptidoglycan but Not Purified LPS Stimulate the Drosophila IMD Pathway
Open this publication in new window or tab >>Monomeric and Polymeric Gram-Negative Peptidoglycan but Not Purified LPS Stimulate the Drosophila IMD Pathway
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2004 In: Immunity, ISSN 1074-7613, Vol. 20, no 5, 637-649 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24033 (URN)
Note
Part of urn:nbn:se:su:diva-646Available from: 2005-09-06 Created: 2005-09-06Bibliographically approved
5. Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in vitro
Open this publication in new window or tab >>Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in vitro
Show others...
2005 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 102, no 18, 6455-6460 p.Article in journal (Refereed) Published
Abstract [en]

Drosophila knockout mutants have placed peptidoglycan recognition proteins (PGRPs) in the two major pathways controlling immune gene expression. We now examine PGRP affinities for peptidoglycan. PGRP-SA and PGRP-LCx are bona fide pattern recognition receptors, and PGRP-SA, the peptidoglycan receptor of the Toll/Dif pathway, has selective affinity for different peptidoglycans. PGRP-LCx, the default peptidoglycan receptor of the Imd/Relish pathway, has strong affinity for all polymeric peptidoglycans tested and for monomeric peptidoglycan. PGRP-LCa does not have affinity for polymeric or monomeric peptidoglycan. Instead, PGRP-LCa can form heterodimers with LCx when the latter is bound to monomeric peptidoglycan. Hence, PGRP-LCa can be said to function as an adaptor, thus adding a new function to a member of the PGRP family.

Identifiers
urn:nbn:se:su:diva-20028 (URN)10.1073/pnas.0407559102 (DOI)15843462 (PubMedID)
Available from: 2007-11-21 Created: 2007-11-21 Last updated: 2017-12-13Bibliographically approved

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