Cocaprin (a β-trefoil fold lectin) from the mushroom Coprinopsis cinerea inhibits both cysteine and aspartic proteases

A group from Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia, etc. has reported that a lectin with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, inhibits both cysteine and aspartic proteases.

Sequence-based structural analysis about Coprinopsis cinerea predicted that the two encoded proteins, CCP1 and CCP2, respectively, and their paralog CCP3, containing a Ricin-type β-trefoil lectin-like domain. All three proteins lack a signal peptide for classical secretion and are, thus, predicted to be cytoplasmic.

It was found that cocaprins inhibit plant cysteine proteases belonging to the C1 family with Ki in the low micromolar range, and also inhibit aspartic protease pepsin with Ki in the low micromolar range.

It has shown that cocaprins have lectin activity in addition to protease inhibition. Glycan microarrays were used to analyze carbohydrate binding specificity of cocaprins. For CCP1, very weak binding was observed on a mammalian glycan array to structures including LacNAc or polyLacNAc and for CCP2 the binding was even weaker. This shows a potential for glycan-binding activity in cocaprins.

However, the biological function of cocaprins is unknown. Regarding a potential role in defense, it is noteworthy that CCP2 expression was induced upon challenge with a fungivorous nematode . However, no toxicity of the protein was detected against nematodes or dipteran insect larvae, although all of which have been shown to be targeted by other β-trefoil protease inhibitors and lectins. Strange isn’t it.