Cospin [PIC1]
editis a serine protease inhibitor from the mushroom species Coprinopsis cinerea in the phylum Basidiomycota. Cospin has similar biochemical properties to other well characterized fungal serine protease inhibitors of family I66 in the MEROPS classification [1-4]. Cospin is one of the few serine protease inhibitors of basidiomycete that have been isolated and characterized.[5] It is highly expressed in sexual reproductive structures termed fruiting bodies and has been cloned and characterized at the molecular and functional levels.
Genetic background
editThe cospin PIC 1 gene sequence isolated from fruiting bodies of the C. cinerea strain AmutBmut can be found under GenBank TM accession number ACX48485 [6].
Biochemical properties
editCospin is a small protein and a highly specific trypsin inhibitor. pH stability Recombinant purified Cospin has been found to remain active after incubation in acidic pH 3 and alkaline pH 11 conditions. [6] Crystal structure Cospin is based on a β-trefoil fold [6] The cospin fold resembles a tree-like structure with 2 loops in the root region, a stem comprising a six-stranded β-barrel, and two layers of loops in the crown region.[6] Cospin, is the first fungal trypsin inhibitor with a determined 3D structure, it utilizes a different loop for trypsin inhibition compared to other beta-trefoil inhibitors.[7] Substrate binding“cospin is a classic inhibitor that binds to the active site in a substrate-like manner and forms a tight and stable complex with trypsin.”[6]. Cospin biotoxicity is not lethal to amoeba A.castellanii, nematode Caenorhabditis elegans, and two true fly species. The toxicity caused developmental delay in both pupae and flies.[6]
Application
editCospin plays a defensive role against predators and parasites[A]. Cospin toxicity targets specifically fruit fly D. melanogaster.[7] Cospin represents one type of fungal protein mediated defence against fungivorous insects.[6] Cospin a serine protease inhibitor can be of use in various applications ranging from pest management, crop protection to drug development, design for therapeutics, and basic medical research.[6]
References
edit- ^ Rawlings N. D. (2010) Peptidase inhibitors in the MEROPS database. Biochimie 92, 1463–1483 [PubMed] (4)
- ^ Kudryavtseva O., Dunaevsky Y., Kamzolkina O., Belozersky M. (2008) Fungal proteolytic enzymes: Features of the extracellular proteases of xylotrophic basidiomycetes. Microbiology 77, 643–653
- ^ Nakamura M., Iketani A., Shioi Y. [2011] A survey of proteases in edible mushrooms with synthetic peptides as substrates. Mycoscience 52, 234–241
- ^ Odani S., Tominaga K., Kondou S., Hori H., Koide T., Hara S., Isemura M., Tsunasawa S. (1999) The inhibitory properties and primary structure of a novel serine proteinase inhibitor from the fruiting body of the basidiomycete, Lentinus edodes. Eur. J. Biochem. 262, 915–923 PubMed (8)
- ^ Sabotic J., Trcek T., Popovic T., Brzin J. (2007) Basidiomycetes harbor a hidden treasure of proteolytic diversity. J. Biotechnol. 128, 297–307 PubMed (1)
- ^ Sabotič J, Bleuler-Martinez S, Renko M, et al. Structural Basis of Trypsin Inhibition and Entomotoxicity of Cospin, Serine Protease Inhibitor Involved in Defense of Coprinopsis cinerea Fruiting Bodies. The Journal of Biological Chemistry. 2012;287(6):3898-3907. (A)
- ^ Sasakawa H., Yoshinaga S., Kojima S., Tamura A. (2002): Structure of POIA1, a homologous protein to the propeptide of subtilisin. Implication for protein foldability and the function as an intramolecular chaperone. J. Mol. Biol. 317, 159–167. (49)