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dc.contributor.authorBeckmann, A-M
dc.contributor.authorGlebov, Konstantin
dc.contributor.authorWalter, J
dc.contributor.authorMerkel, O
dc.contributor.authorMangold, M
dc.contributor.authorSchmidt, F
dc.contributor.authorBecker-Pauly, C
dc.contributor.authorGütschow, M
dc.contributor.authorStirnberg, M
dc.date.accessioned2019-01-30T12:50:05Z
dc.date.available2019-01-30T12:50:05Z
dc.date.issued2016-08-01
dc.identifier.issn1431-6730
dc.identifier.issn1437-4315
dc.identifier.urihttp://hdl.handle.net/10026.1/13240
dc.description.abstract

<jats:title>Abstract</jats:title><jats:p>Proteolytic processing of the amyloid precursor protein (APP) leads to amyloid-β (Aβ) peptides. So far, the mechanism of APP processing is insufficiently characterized at the molecular level. Whereas the knowledge of Aβ generation by several proteases has been expanded, the contribution of the Kunitz-type protease inhibitor domain (KPI) present in two major APP isoforms to the complex proteolytic processing of APP is poorly understood. In this study, we have identified KPI-containing APP as a very potent, slow-binding inhibitor for the membrane-bound proteolytic regulator of iron homeostasis matriptase-2 by forming stable complexes with its target protease in HEK cells. Inhibition and complex formation depend on the intact KPI domain. By inhibiting matriptase-2, KPI-containing APP is protected from matriptase-2-mediated proteolysis within the Aβ region, thus preventing the generation of N-terminally truncated Aβ.</jats:p>

dc.format.extent777-790
dc.format.mediumPrint
dc.languageeng
dc.language.isoen
dc.publisherDe Gruyter
dc.subjectamyloid beta; enzyme kinetics
dc.subjectiron homeostasis
dc.subjectKunitz inhibitor
dc.subjecttype II transmembrane serine protease
dc.titleThe intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000379513800007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue8
plymouth.volume397
plymouth.publication-statusPublished
plymouth.journalBiological Chemistry
dc.identifier.doi10.1515/hsz-2015-0263
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeGermany
dcterms.dateAccepted2016-04-11
dc.identifier.eissn1437-4315
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1515/hsz-2015-0263
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-08-01
rioxxterms.typeJournal Article/Review


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