| Structural and functional characterization of a highly specific serpin in the insect innate immunity. | |
| | |
MedLine Citation:
|
PMID: 21047786 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The 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, Spätzle-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 β-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 Spätzle-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. |
| | |
Authors:
|
Sun Hee Park; Rui Jiang; Shunfu Piao; Bing Zhang; Eun-Hye Kim; Hyun-Mi Kwon; Xiao Ling Jin; Bok Luel Lee; Nam-Chul Ha |
Related Documents
:
|
10854846 - Application of linear free energy relationships to the serpin-proteinase inhibition mec... 1620346 - Protease nexin i, thrombin- and urokinase-inhibiting serpin, concentrated in normal hum... 21401056 - Electroactive multilayer assemblies of bilirubin oxidase and human cytochrome c mutants... 14698626 - Production, characterization, and use of serpin antibodies. 16408036 - Dynamic imaging of protease activity with fluorescently quenched activity-based probes. 12795596 - Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate synth... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-03 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-01-10 Completed Date: 2011-03-02 Revised Date: 2012-01-16 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 1567-75 Citation Subset: IM |
Affiliation:
|
College of Pharmacy and Research Institute for Drug Development, Pusan National University, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
PDB/3OZQ |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Antithrombins / chemistry, metabolism Binding Sites / genetics, immunology Calcium / metabolism Crystallography Enzyme Activation / immunology Heparin / metabolism Humans Immunity, Innate / physiology* Molecular Sequence Data Mutagenesis, Site-Directed Protein Structure, Tertiary Serpins* / genetics, immunology, metabolism Signal Transduction / immunology Structure-Activity Relationship Substrate Specificity Tenebrio / enzymology*, immunology* Toll-Like Receptors / immunology, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Antithrombins; 0/Serpins; 0/Toll-Like Receptors; 7440-70-2/Calcium; 9005-49-6/Heparin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inhibition of Arabidopsis O-acetylserine(thiol)lyase A1 by tyrosine nitration.
Next Document: Cog2 null mutant CHO cells show defective sphingomyelin synthesis.