Clustering of peptidoglycan recognition protein-SA is required for sensing lysine-type peptidoglycan in insects.
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.
Park
Ji-Won
JW
National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Kim
Chan-Hee
CH
Kim
Jung-Hyun
JH
Je
Byung-Rok
BR
Roh
Kyung-Baeg
KB
Kim
Su-Jin
SJ
Lee
Hyeon-Hwa
HH
Ryu
Ji-Hwan
JH
Lim
Jae-Hong
JH
Oh
Byung-Ha
BH
Lee
Won-Jae
WJ
Ha
Nam-Chul
NC
Lee
Bok-Luel
BL
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
D002352:Carrier Proteins; D004792:Enzyme Precursors; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein; C038451:pro-phenoloxidase; D004156:Catechol Oxidase; D008239:Lysine