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

Journal article

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: Wang, L; Weber, A; Atilano, M; Filipe, SR; Gay, N

• Publication status: Published
• Journal: EMBO journal
• Volume: 25
• Issue: 20
• Pages: 5005-5014
• Publication date: 2006-10-01
• DOI: 10.1038/sj.emboj.7601363
• EISSN: 1460-2075
• ISSN: 0261-4189
• Language: English
• Keywords: Peptidoglycan; Drosophila melanogaster; Animals; Antigen Presentation; Signal Transduction; Gram-Positive Bacterial Infections; Drosophila Proteins; Gram-Positive Bacteria; Carrier Proteins