title: Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA.
abstract: Genetic evidence indicates that Drosophila defense against Gram-positive bacteria is mediated by two putative pattern recognition receptors acting upstream of Toll, namely Gram-negative binding protein 1 (GNBP1) and peptidoglycan recognition protein SA (PGRP-SA). Until now however, the molecular recognition proceedings for sensing of Gram-positive pathogens were not known. In the present, we report the physical interaction between GNBP1 and PGRP-SA using recombinant proteins. GNBP1 was able to hydrolyze Gram-positive peptidoglycan (PG), while PGRP-SA bound highly purified PG fragments (muropeptides). Interaction between these proteins was enhanced in the presence of PG or muropeptides. PGRP-SA binding depended on the polymerization status of the muropeptides, pointing to constraints in the number of PGRP-SA molecules bound for signaling initiation. We propose a model whereby GNBP1 presents a processed form of PG for sensing by PGRP-SA and that a tripartite interaction between these proteins and PG is essential for downstream signaling.
authors.affiliation: Genetics Unit, Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.forename: Alexander N R
authors.initials: AN
authors.lastname: Weber
authors.forename: Magda L
authors.initials: ML
authors.lastname: Atilano
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Filipe
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Gay
authors.forename: Petros
authors.initials: P
authors.lastname: Ligoxygakis
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004331:Drosophila melanogaster; D006094:Gram-Positive Bacteria / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010457:Peptidoglycan / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C480085:Gnbp1 protein, Drosophila; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein