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  • The EMBO Journal (2006) 25, 5005 - 5014
  • doi:10.1038/sj.emboj.7601363

Published online: 5 October 2006

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

Lihui Wang1, Alexander NR Weber2,a, Magda L Atilano3, Sergio R Filipe3, Nicholas J Gay2 and Petros Ligoxygakis1

  1. Genetics Unit, Department of Biochemistry, University of Oxford, Oxford, UK
  2. Department of Biochemistry, University of Cambridge, Cambridge, UK
  3. Instituto de Tecnologia Química e Biológica/Universidade Nova de Lisboa, Av. da República (EAN), Oeiras, Portugal

Correspondence to:

Petros Ligoxygakis, Genetics Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, Oxfordshire OX1 3QU, UK. Tel.: +44 1865 275314; Fax: +44 1865 275318; E-mail: petros.ligoxygakis@bioch.ox.ac.uk

aPresent address: German Cancer Research Centre, Im Neuenheimer Feld, 69120 Heidelberg, Germany

Received 23 January 2006; Accepted 17 August 2006

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.

  • Keywords:

    • Drosophila,
    • innate immunity,
    • non-self-recognition