The macromolecular assembly of pathogen-recognition receptors is impelled by serine proteases, via their complement control protein modules.
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.
Le Saux
Agnès
A
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
Ng
Patricia Miang Lon
PM
Koh
Joanne Jing Yun
JJ
Low
Diana Hooi Ping
DH
Leong
Geraldine E-Ling
GE
Ho
Bow
B
Ding
Jeak Ling
JL
D000595:Amino Acid Sequence; D000818:Animals; D060829:Arthropod Proteins; D002097:C-Reactive Protein / Q000378:metabolism*; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D004792:Enzyme Precursors / Q000276:immunology*; D037161:Galectins / Q000378:metabolism*; D006458:Hemolymph / Q000378:metabolism / Q000382:microbiology; D006737:Horseshoe Crabs / Q000201:enzymology* / Q000276:immunology; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D060829:Arthropod Proteins; D004792:Enzyme Precursors; D037161:Galectins; D003165:Complement System Proteins; D002097:C-Reactive Protein; D012697:Serine Endopeptidases; C057151:Limulus clotting factor C