Matches in SemOpenAlex for { <https://semopenalex.org/work/W2060807002> ?p ?o ?g. }
- W2060807002 endingPage "2656" @default.
- W2060807002 startingPage "2646" @default.
- W2060807002 abstract "γ-Secretase is a multisubunit protease complex that is responsible for generating amyloid-β peptides, which are associated with Alzheimer disease. The catalytic subunit of γ-secretase is presenilin 1 (PS1), which contains an initial substrate-binding site that is distinct from the catalytic site. Processive cleavage is suggested in the intramembrane-cleaving mechanism of γ-secretase. However, it largely remains unknown as to how γ-secretase recognizes its substrate during proteolysis. Here, we identified that the α-helical structural region of hydrophilic loop 1 (HL1) and the C-terminal region of human PS1 are distinct substrate-binding sites. Mutational analyses revealed that substrate binding to the HL1 region is critical for both ε- and γ-cleavage, whereas binding to the C-terminal region hampers γ-cleavage. Moreover, we propose that substrate binding triggers conformational changes in PS1, rendering it suitable for catalysis. Our data provide new insights into the complicated catalytic mechanism of PS1." @default.
- W2060807002 created "2016-06-24" @default.
- W2060807002 creator A5001818206 @default.
- W2060807002 creator A5002714615 @default.
- W2060807002 creator A5032254037 @default.
- W2060807002 creator A5068878520 @default.
- W2060807002 creator A5074331541 @default.
- W2060807002 creator A5074597662 @default.
- W2060807002 creator A5088214193 @default.
- W2060807002 creator A5090117851 @default.
- W2060807002 date "2015-02-11" @default.
- W2060807002 modified "2023-10-18" @default.
- W2060807002 title "Cooperative Roles of Hydrophilic Loop 1 and the C-Terminus of Presenilin 1 in the Substrate-Gating Mechanism of -Secretase" @default.
- W2060807002 cites W1490438386 @default.
- W2060807002 cites W1547581699 @default.
- W2060807002 cites W1552188451 @default.
- W2060807002 cites W1592442520 @default.
- W2060807002 cites W1638783749 @default.
- W2060807002 cites W1891797303 @default.
- W2060807002 cites W1965013631 @default.
- W2060807002 cites W1966686696 @default.
- W2060807002 cites W1967679941 @default.
- W2060807002 cites W1967785399 @default.
- W2060807002 cites W1970552333 @default.
- W2060807002 cites W1971576227 @default.
- W2060807002 cites W1978560720 @default.
- W2060807002 cites W1978566291 @default.
- W2060807002 cites W1980666220 @default.
- W2060807002 cites W1981860609 @default.
- W2060807002 cites W1982825693 @default.
- W2060807002 cites W1982963671 @default.
- W2060807002 cites W1984300869 @default.
- W2060807002 cites W1986443184 @default.
- W2060807002 cites W1988320562 @default.
- W2060807002 cites W1990102556 @default.
- W2060807002 cites W2002093986 @default.
- W2060807002 cites W2005483591 @default.
- W2060807002 cites W2013782136 @default.
- W2060807002 cites W2025911651 @default.
- W2060807002 cites W2026596383 @default.
- W2060807002 cites W2029298729 @default.
- W2060807002 cites W2038917939 @default.
- W2060807002 cites W2048048305 @default.
- W2060807002 cites W2050586736 @default.
- W2060807002 cites W2055746125 @default.
- W2060807002 cites W2058571820 @default.
- W2060807002 cites W2060178110 @default.
- W2060807002 cites W2060575929 @default.
- W2060807002 cites W2067354786 @default.
- W2060807002 cites W2070068402 @default.
- W2060807002 cites W2070164943 @default.
- W2060807002 cites W2073420511 @default.
- W2060807002 cites W2075829521 @default.
- W2060807002 cites W2081256532 @default.
- W2060807002 cites W2085380780 @default.
- W2060807002 cites W2088989293 @default.
- W2060807002 cites W2089341968 @default.
- W2060807002 cites W2089710618 @default.
- W2060807002 cites W2095460718 @default.
- W2060807002 cites W2097750046 @default.
- W2060807002 cites W2107824265 @default.
- W2060807002 cites W2127637662 @default.
- W2060807002 cites W2129787742 @default.
- W2060807002 cites W2142044194 @default.
- W2060807002 cites W2142529984 @default.
- W2060807002 cites W2158411892 @default.
- W2060807002 cites W2162220128 @default.
- W2060807002 cites W2322877829 @default.
- W2060807002 cites W2833026885 @default.
- W2060807002 doi "https://doi.org/10.1523/jneurosci.3164-14.2015" @default.
- W2060807002 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6605612" @default.
- W2060807002 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25673856" @default.
- W2060807002 hasPublicationYear "2015" @default.
- W2060807002 type Work @default.
- W2060807002 sameAs 2060807002 @default.
- W2060807002 citedByCount "47" @default.
- W2060807002 countsByYear W20608070022015 @default.
- W2060807002 countsByYear W20608070022016 @default.
- W2060807002 countsByYear W20608070022017 @default.
- W2060807002 countsByYear W20608070022018 @default.
- W2060807002 countsByYear W20608070022019 @default.
- W2060807002 countsByYear W20608070022020 @default.
- W2060807002 countsByYear W20608070022021 @default.
- W2060807002 countsByYear W20608070022022 @default.
- W2060807002 countsByYear W20608070022023 @default.
- W2060807002 crossrefType "journal-article" @default.
- W2060807002 hasAuthorship W2060807002A5001818206 @default.
- W2060807002 hasAuthorship W2060807002A5002714615 @default.
- W2060807002 hasAuthorship W2060807002A5032254037 @default.
- W2060807002 hasAuthorship W2060807002A5068878520 @default.
- W2060807002 hasAuthorship W2060807002A5074331541 @default.
- W2060807002 hasAuthorship W2060807002A5074597662 @default.
- W2060807002 hasAuthorship W2060807002A5088214193 @default.
- W2060807002 hasAuthorship W2060807002A5090117851 @default.
- W2060807002 hasBestOaLocation W20608070021 @default.
- W2060807002 hasConcept C104292427 @default.
- W2060807002 hasConcept C104317684 @default.
- W2060807002 hasConcept C107824862 @default.