3OZQ
Crystal structure of Serpin48, which is a highly specific serpin in the insect Tenebrio molitor
Summary for 3OZQ
| Entry DOI | 10.2210/pdb3ozq/pdb |
| Related | 3NS3 |
| Descriptor | Serpin48 (2 entities in total) |
| Functional Keywords | serpin, serpin48 inhibits spe specifically, spe, hydrolase inhibitor |
| Biological source | Tenebrio molitor (Yellow mealworm) |
| Total number of polymer chains | 1 |
| Total formula weight | 42226.26 |
| Authors | Park, S.H.,Piao, S.,Ha, N.-C. (deposition date: 2010-09-27, release date: 2010-10-27, Last modification date: 2024-03-20) |
| Primary citation | Park, S.H.,Jiang, R.,Piao, S.,Zhang, B.,Kim, E.H.,Kwon, H.M.,Jin, X.L.,Lee, B.L.,Ha, N.-C. Structural and functional characterization of a highly specific serpin in the insect innate immunity J.Biol.Chem., 286:1567-1575, 2011 Cited by PubMed Abstract: 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. PubMed: 21047786DOI: 10.1074/jbc.M110.144006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
Download full validation report
