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Crystal structure of Serpin48, which is a highly specific serpin in the insect Tenebrio molitorCrystal structure of Serpin48, which is a highly specific serpin in the insect Tenebrio molitor
Structural highlights
Publication Abstract from PubMedThe Toll signaling pathway, an essential innate immune response in invertebrates, is mediated via the serine protease cascade. Once activated, the serine proteases are irreversibly inactivated by serine protease inhibitors (serpins). Recently, we identified three serpin-serine protease pairs that are directly involved in the regulation of Toll signaling cascade in a large beetle, Tenebrio molitor. Of these, the serpin SPN48 was cleaved by its target serine protease, Spatzle-processing enzyme, at a noncanonical P1 residue of the serpin's reactive center loop. To address this unique cleavage, we report the crystal structure of SPN48, revealing that SPN48 exhibits a native conformation of human antithrombin, where the reactive center loop is partially inserted into the center of the largest beta-sheet of SPN48. The crystal structure also shows that SPN48 has a putative heparin-binding site that is distinct from those of the mammalian serpins. Ensuing biochemical studies demonstrate that heparin accelerates the inhibition of Spatzle-processing enzyme by a proximity effect in targeting the SPN48. Our finding provides the molecular mechanism of how serpins tightly regulate innate immune responses in invertebrates. Structural and functional characterization of a highly specific serpin in the insect innate immunity.,Park SH, Jiang R, Piao S, Zhang B, Kim EH, Kwon HM, Jin XL, Lee BL, Ha NC J Biol Chem. 2011 Jan 14;286(2):1567-75. Epub 2010 Nov 3. PMID:21047786[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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