Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA

• Published in: The EMBO journal 2006-10, Vol.25 (20), p.5005-5014
• Main Authors: Wang, L, Weber, A.N.R, Atilano, M.L, Filipe, S.R, Gay, N.J, Ligoxygakis, P
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - genetics; Antigen Presentation - immunology; Bacteria; bacterial infections; binding capacity; binding proteins; Carrier Proteins - genetics; Carrier Proteins - immunology; Carrier Proteins - metabolism; disease resistance; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - immunology; Drosophila Proteins - metabolism; EMBO19; EMBO23; Genetics; glycoproteins; Gram-positive bacteria; Gram-Positive Bacteria - genetics; Gram-Positive Bacteria - immunology; Gram-Positive Bacteria - metabolism; Gram-Positive Bacterial Infections - genetics; Gram-Positive Bacterial Infections - immunology; Gram-Positive Bacterial Infections - metabolism; hydrolases; hydrolysis; innate immunity; insect proteins; Insects; muropeptides; non-self-recognition; Pathogens; Pattern recognition; Peptides; Peptidoglycan - immunology; Peptidoglycan - metabolism; peptidoglycans; Proteins; Signal transduction; Signal Transduction - genetics; Signal Transduction - immunology; Upstream
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7601363

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.