93-kDa Twin-domain Serine Protease Inhibitor (Serpin) Has a Regulatory Function on the Beetle Toll Proteolytic Signaling Cascade

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Serpins are protease inhibitors that play essential roles in the down-regulation of extracellular proteolytic cascades. The core serpin domain is highly conserved, and typical serpins are encoded with a molecular size of 35-50 kDa. Here, we describe a novel 93-kDa protein that contains two complete, tandemly arrayed serpin domains. This twin serpin, SPN93, was isolated from the larval hemolymph of the large beetle Tenebrio molitor. The N-terminal serpin domain of SPN93 forms a covalent complex with the Spatzle-processing enzyme, a terminal serine protease of the Toll signaling cascade, whereas the C-terminal serpin domain of SPN93 forms complexes with a modular serine protease and the Spatzle-processing enzyme-activating enzyme, which are two different enzymes of the cascade. Consequently, SPN93 inhibited beta-1,3-glucan-mediated Toll proteolytic cascade activation in an in vitro system. Site-specific proteolysis of SPN93 at the N-terminal serpin domain was observed after activation of the Toll proteolytic cascade in vivo, and down-regulation of SPN93 by RNAi sensitized beta-1,3-glucan-mediated larval death. Therefore, SPN93 is the first serpin that contains twin tandemly arrayed and functionally active serpin domains that have a regulatory role in the larval Toll proteolytic signaling cascade.
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Issue Date
2011-10
Language
English
Article Type
Article
Keywords

FUNGAL-INFECTIONS; CRYSTAL-STRUCTURE; DROSOPHILA; ACTIVATION; INSECT; PEPTIDOGLYCAN; MELANIZATION; RECOGNITION; PATHWAY; MECHANISM

Citation

JOURNAL OF BIOLOGICAL CHEMISTRY, v.286, no.40, pp.35087 - 35095

ISSN
0021-9258
URI
http://hdl.handle.net/10203/95431
Appears in Collection
CH-Journal Papers(저널논문)
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