The macromolecular assembly of pathogen-recognition receptors is impelled by serine proteases, via their complement control protein modules |
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Authors: | Le Saux Agnès Ng Patricia Miang Lon Koh Joanne Jing Yun Low Diana Hooi Ping Leong Geraldine E-Ling Ho Bow Ding Jeak Ling |
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Affiliation: | 1 Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore 2 NanoBioanalytics Laboratory, Faculty of Engineering, National University of Singapore, Singapore 117574, Singapore 3 Singapore-MIT Alliance, Computational Systems Biology, Singapore 117576, Singapore 4 Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore |
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Abstract: | Although the innate immune response is triggered by the formation of a stable assembly of pathogen-recognition receptors (PRRs) onto the pathogens, the driving force that enables this PRR-PRR interaction is unknown. Here, we show that serine proteases, which are activated during infection, participate in associating with the PRRs. Inhibition of serine proteases gravely impairs the PRR assembly. Using yeast two-hybrid and pull-down methods, we found that two serine proteases in the horseshoe crab Carcinoscorpius rotundicauda are able to bind to the following three core members of PRRs: galactose-binding protein, Carcinolectin-5 and C-reactive protein. These two serine proteases are (1) Factor C, which activates the coagulation pathway, and (2) C2/Bf, a protein from the complement pathway. By systematic molecular dissection, we show that these serine proteases interact with the core “pathogen-recognition complex” via their complement control protein modules. |
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Keywords: | PRR, pathogen-recognition receptor LPS, lipopolysaccharide CRP, C-reactive protein CL5, Carcinolectin-5 GBP, galactose-binding protein Tryp-SP, trypsin-like serine protease FC, Factor C CCP, complement control protein GlcNAc, N-acetylglucosamine MS, mass spectrometry TBS, Tris-buffered saline QDO, quadruple dropout GST, glutathione S-transferase SC, synthetic complete |
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