2cm9
The complement inhibitor OmCI in complex with ricinoleic acid
Structural highlights
FunctionC5I_ORNMO Bifunctional protein derived from blood-feeding ticks that specifically prevents complement-mediated C5 activation and acts as a scavenger for inflammatory modulators such as leukotriene B4 (LTB4). C5 and LTB4 binding activities are independent (PubMed:23625922). Inhibits classical and alternative pathways of complement activation by preventing the cleavage of complement C5 by both classical and alternative C5 convertases (PubMed:15699138) (Probable). Inhibits complement in all species tested (rabbit, rat, guinea pig, mouse, pig, and human) (PubMed:27018802). Also binds fatty acids such as palmitoleic acid and ricinoleic acid, as well as inflammatory modulators LTB4 (and presumably arachidonic acid (AA)) that may be sequestered to interfere with the host inflammatory response (PubMed:23625922). Does not bind to leukotriene C4 and thromboxane B2 (PubMed:23625922). In vivo, when tested on the mouse model of immune complex-induced acute lung injury (IC-ALI), shows a potent inhibitory activity of the pathology, equally dependent on both C5 inhibition and LTB4 binding for full activity (PubMed:23625922).[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site. The structure of OMCI, a novel lipocalin inhibitor of the complement system.,Roversi P, Lissina O, Johnson S, Ahmat N, Paesen GC, Ploss K, Boland W, Nunn MA, Lea SM J Mol Biol. 2007 Jun 8;369(3):784-93. Epub 2007 Mar 30. PMID:17445829[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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