Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea.
Authors
Renko, Miha
Plaza, David F
Schmieder, Stefanie S
Künzler, Markus
Publication Date
2022-04-28Journal Title
Int J Mol Sci
ISSN
1422-0067
Publisher
MDPI AG
Volume
23
Issue
9
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Renko, M., Zupan, T., Plaza, D. F., Schmieder, S. S., Perišić Nanut, M., Kos, J., Turk, D., et al. (2022). Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea.. Int J Mol Sci, 23 (9) https://doi.org/10.3390/ijms23094916
Abstract
We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with Ki in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with Ki in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.
Keywords
protease inhibitor, cysteine protease, aspartic protease, β-trefoil fold
Sponsorship
Slovenian Research Agency (J4-9299, J4-1771, P1-0048, P4-0127, P4-0432)
Swiss National Science Foundation (31003A_149512)
European Molecular Biology Organization (ASTF 317-2010)
Identifiers
External DOI: https://doi.org/10.3390/ijms23094916
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336653
Rights
Licence:
https://creativecommons.org/licenses/by/4.0/
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