Publication Abstract from PubMed
Cospin (PIC1) from Coprinopsis cinerea is a serine protease inhibitor with biochemical properties similar to those of the previously characterized fungal serine protease inhibitors, cnispin from Clitocybe nebularis and LeSPI from Lentinus edodes, classified in the family I66 of the MEROPS protease inhibitor classification. In particular, it exhibits a highly specific inhibitory profile as a very strong inhibitor of trypsin with K(i) in the picomolar range. Determination of the crystal structure revealed that the protein has a beta-trefoil fold. Site-directed mutagenesis and mass spectrometry results have confirmed Arg-27 as the reactive binding site for trypsin inhibition. The loop containing Arg-27 is positioned between the beta2 and beta3 strands, distinguishing cospin from other beta-trefoil-fold serine protease inhibitors in which beta4-beta5 or beta5-beta6 loops are involved in protease inhibition. Biotoxicity assays of cospin on various model organisms revealed a strong and specific entomotoxic activity against Drosophila melanogaster. The inhibitory inactive R27N mutant was not entomotoxic, associating toxicity with inhibitory activity. Along with the abundance of cospin in fruiting bodies of C. cinerea and the lack of trypsin-like proteases in the C. cinerea genome, these results suggest that cospin and its homologs are effectors of a fungal defense mechanism against fungivorous insects that function by specific inhibition of serine proteases in the insect gut.
Structural Basis of Trypsin Inhibition and Entomotoxicity of Cospin, Serine Protease Inhibitor Involved in Defense of Coprinopsis cinerea Fruiting Bodies.,Sabotic J, Bleuler-Martinez S, Renko M, Avanzo Caglic P, Kallert S, Strukelj B, Turk D, Aebi M, Kos J, Kunzler M J Biol Chem. 2012 Feb 3;287(6):3898-907. Epub 2011 Dec 13. PMID:22167196[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
