Show simple item record

dc.contributor.authorRenko, Miha
dc.contributor.authorZupan, Tanja
dc.contributor.authorPlaza, David F
dc.contributor.authorSchmieder, Stefanie S
dc.contributor.authorPerišić Nanut, Milica
dc.contributor.authorKos, Janko
dc.contributor.authorTurk, Dušan
dc.contributor.authorKünzler, Markus
dc.contributor.authorSabotič, Jerica
dc.date.accessioned2022-04-30T08:00:04Z
dc.date.available2022-04-30T08:00:04Z
dc.date.issued2022-04-28
dc.identifier.issn1422-0067
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336653
dc.description.abstractWe 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.
dc.languageen
dc.publisherMDPI AG
dc.subjectprotease inhibitor
dc.subjectcysteine protease
dc.subjectaspartic protease
dc.subjectβ-trefoil fold
dc.titleCocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea.
dc.typeArticle
dc.date.updated2022-04-30T08:00:03Z
prism.issueIdentifier9
prism.publicationNameInt J Mol Sci
prism.volume23
dc.identifier.doi10.17863/CAM.84074
dcterms.dateAccepted2022-04-26
rioxxterms.versionofrecord10.3390/ijms23094916
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidZupan, Tanja [0000-0003-2336-0634]
dc.contributor.orcidPerišić Nanut, Milica [0000-0003-2314-2733]
dc.contributor.orcidKos, Janko [0000-0002-4228-3518]
dc.contributor.orcidTurk, Dušan [0000-0003-0205-6609]
dc.contributor.orcidSabotič, Jerica [0000-0002-2404-0192]
dc.identifier.eissn1422-0067
pubs.funder-project-idSlovenian Research Agency (J4-9299, J4-1771, P1-0048, P4-0127, P4-0432)
pubs.funder-project-idSwiss National Science Foundation (31003A_149512)
pubs.funder-project-idEuropean Molecular Biology Organization (ASTF 317-2010)
cam.issuedOnline2022-04-28


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record