title: Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects.
abstract: Recognition of lysine-type peptidoglycan by peptidoglycan recognition protein (PGRP)-SA provokes the activation of the Toll and prophenoloxidase pathways. Here we reveal that a soluble fragment of lysine-type peptidoglycan, a long glycan chain with short stem peptides, is a potent activator of the Drosophila Toll pathway and the prophenoloxidase activation cascade in the beetle Tenebrio molitor. Using this peptidoglycan fragment, we present biochemical evidence that clustering of PGRP-SA molecules on the peptidoglycan is required for the activation of the prophenoloxidase cascade. We subsequently highlight that the lysozyme-mediated partial digestion of highly cross-linked lysine-type peptidoglycan dramatically increases the binding of PGRP-SA, presumably by inducing clustering of PGRP-SA, which then recruits the Gram-negative bacteria-binding protein 1 homologue and a modular serine protease containing low-density lipoprotein and complement control protein domains. The crucial role of lysozyme in the prophenoloxidase activation cascade is further confirmed in vivo by using a lysozyme inhibitor. Taken together, we propose a model whereby lysozyme presents a processed form of lysine-type peptidoglycan for clustering of PGRP-SA that recruits Gram-negative bacteria-binding protein 1 and the modular serine protease, which leads to the activation of both the Toll and prophenoloxidase pathways.
authors.affiliation: National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Chan-Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Byung-Rok
authors.initials: BR
authors.lastname: Je
authors.forename: Kyung-Baeg
authors.initials: KB
authors.lastname: Roh
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyeon-Hwa
authors.initials: HH
authors.lastname: Lee
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lim
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Ha
authors.forename: Bok-Luel
authors.initials: BL
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004156:Catechol Oxidase / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D004792:Enzyme Precursors; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein; C038451:pro-phenoloxidase; D004156:Catechol Oxidase; D008239:Lysine