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    Structure and Function of the γ-Secretase Complex

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    Available after June 14, 2020 (2.622Mb)
    Issue Date
    2019-06-14
    Author
    Wolfe, Michael S.
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2019 American Chemical Society
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    Abstract
    γ-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.
    Description
    This 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.
    URI
    http://hdl.handle.net/1808/29732
    DOI
    https://doi.org/10.1021/acs.biochem.9b00401
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    • Medicinal Chemistry Scholarly Works [244]
    Citation
    Wolfe M. S. (2019). Structure and Function of the γ-Secretase Complex. Biochemistry, 58(27), 2953–2966. doi:10.1021/acs.biochem.9b00401

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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