The intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2
dc.contributor.author | Beckmann, A-M | |
dc.contributor.author | Glebov, Konstantin | |
dc.contributor.author | Walter, J | |
dc.contributor.author | Merkel, O | |
dc.contributor.author | Mangold, M | |
dc.contributor.author | Schmidt, F | |
dc.contributor.author | Becker-Pauly, C | |
dc.contributor.author | Gütschow, M | |
dc.contributor.author | Stirnberg, M | |
dc.date.accessioned | 2019-01-30T12:50:05Z | |
dc.date.available | 2019-01-30T12:50:05Z | |
dc.date.issued | 2016-08-01 | |
dc.identifier.issn | 1431-6730 | |
dc.identifier.issn | 1437-4315 | |
dc.identifier.uri | http://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.extent | 777-790 | |
dc.format.medium | ||
dc.language | eng | |
dc.language.iso | en | |
dc.publisher | De Gruyter | |
dc.subject | amyloid beta; enzyme kinetics | |
dc.subject | iron homeostasis | |
dc.subject | Kunitz inhibitor | |
dc.subject | type II transmembrane serine protease | |
dc.title | The intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2 | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000379513800007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 8 | |
plymouth.volume | 397 | |
plymouth.publication-status | Published | |
plymouth.journal | Biological Chemistry | |
dc.identifier.doi | 10.1515/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.place | Germany | |
dcterms.dateAccepted | 2016-04-11 | |
dc.identifier.eissn | 1437-4315 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1515/hsz-2015-0263 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2016-08-01 | |
rioxxterms.type | Journal Article/Review |