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dc.contributor.authorWolfe, Michael S.
dc.date.accessioned2019-11-07T22:08:03Z
dc.date.available2019-11-07T22:08:03Z
dc.date.issued2019-06-14
dc.identifier.citationWolfe M. S. (2019). Structure and Function of the γ-Secretase Complex. Biochemistry, 58(27), 2953–2966. doi:10.1021/acs.biochem.9b00401en_US
dc.identifier.urihttp://hdl.handle.net/1808/29732
dc.descriptionThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.biochem.9b00401.en_US
dc.description.abstractγ-Secretase is a membrane-embedded protease complex, with presenilin as the catalytic component containing two transmembrane aspartates in the active site. With more than 90 known substrates, the γ-secretase complex is considered “the proteasome of the membrane”, with central roles in biology and medicine. The protease carries out hydrolysis within the lipid bilayer to cleave the transmembrane domain of the substrate multiple times before releasing secreted products. For many years, elucidation of γ-secretase structure and function largely relied on small-molecule probes and mutagenesis. Recently, however, advances in cryo-electron microscopy have led to the first detailed structures of the protease complex. Two new reports of structures of γ-secretase bound to membrane protein substrates provide great insight into the nature of substrate recognition and how Alzheimer’s disease-causing mutations in presenilin might alter substrate binding and processing. These new structures offer a powerful platform for elucidating enzyme mechanisms, deciphering effects of disease-causing mutations, and advancing Alzheimer’s disease drug discovery.en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsCopyright © 2019 American Chemical Societyen_US
dc.titleStructure and Function of the γ-Secretase Complexen_US
dc.typeArticleen_US
kusw.kuauthorWolfe, Michael S.
kusw.kudepartmentMedicinal Chemistryen_US
dc.identifier.doi10.1021/acs.biochem.9b00401en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-5721-9092en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC6618299en_US
dc.rights.accessrightsembargoedAccessen_US


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