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• W2298041512 startingPage "1760" @default.
• W2298041512 abstract "Human peptidyl-prolyl isomerase (PPIase) Pin1 plays key roles in developmental processes, cell proliferation, and neuronal function. Extensive phosphorylation of the microtubule binding protein tau has been implicated in neurodegeneration and Alzheimer's disease. For the past 15 years, these two players have been the focus of an enormous research effort to unravel the biological relevance of their interplay in health and disease, resulting in a series of proposed molecular mechanism of how Pin1 catalysis of tau results in biological phenotypes. Our results presented here refute these mechanisms of Pin1 action. Using NMR, isothermal calorimetry (ITC), and small angle x-ray scattering (SAXS), we dissect binding and catalysis on multiple phosphorylated tau with particular emphasis toward the Alzheimer's associated AT180 tau epitope containing phosphorylated THR231 and SER235. We find that phosphorylated (p-) SER235-PRO, but not pTHR231-PRO, is exclusively catalyzed by full-length Pin1 and isolated PPIase domain. Importantly, site-specific measurements of Pin1-catalysis of CDK2/CycA-phosphorylated full-length tau reveal a number of sites that are catalyzed simultaneously with different efficiencies. Furthermore, we show that the turnover efficiency at pSER235 by Pin1 is independent of both the WW domain and phosphorylation on THR231. Our mechanistic results on site-specific binding and catalysis together with the lack of an increase of dephosphorylation rates by PP2A counter a series of previously published models for the role of Pin1 catalysis of tau in Alzheimer's disease. Together, our data reemphasize the complicated scenario between binding and catalysis of multiple phosphorylated tau by Pin1 and the need for directly linking biological phenotypes and residue-specific turnover in Pin1 substrates." @default.
• W2298041512 created "2016-06-24" @default.
• W2298041512 creator A5013637723 @default.
• W2298041512 creator A5018255875 @default.
• W2298041512 creator A5024415307 @default.
• W2298041512 creator A5071376755 @default.
• W2298041512 creator A5085662635 @default.
• W2298041512 date "2016-05-01" @default.
• W2298041512 modified "2023-10-05" @default.
• W2298041512 title "Molecular Mechanism of Pin1–Tau Recognition and Catalysis" @default.
• W2298041512 cites W1541944730 @default.
• W2298041512 cites W1565197201 @default.
• W2298041512 cites W1592377138 @default.
• W2298041512 cites W1599940872 @default.
• W2298041512 cites W1965456320 @default.
• W2298041512 cites W1966078827 @default.
• W2298041512 cites W1968069432 @default.
• W2298041512 cites W1971252951 @default.
• W2298041512 cites W1971696898 @default.
• W2298041512 cites W1974036368 @default.
• W2298041512 cites W1974326515 @default.
• W2298041512 cites W1975317507 @default.
• W2298041512 cites W1979702454 @default.
• W2298041512 cites W1981346588 @default.
• W2298041512 cites W1982126789 @default.
• W2298041512 cites W1982137838 @default.
• W2298041512 cites W1982450769 @default.
• W2298041512 cites W1983741980 @default.
• W2298041512 cites W1985239419 @default.
• W2298041512 cites W1986144447 @default.
• W2298041512 cites W1988903945 @default.
• W2298041512 cites W1989240813 @default.
• W2298041512 cites W1989895869 @default.
• W2298041512 cites W1994794059 @default.
• W2298041512 cites W1997820676 @default.
• W2298041512 cites W2004100939 @default.
• W2298041512 cites W2006413040 @default.
• W2298041512 cites W2007823692 @default.
• W2298041512 cites W2012316183 @default.
• W2298041512 cites W2017342193 @default.
• W2298041512 cites W2017387272 @default.
• W2298041512 cites W2020209643 @default.
• W2298041512 cites W2025438577 @default.
• W2298041512 cites W2025755348 @default.
• W2298041512 cites W2027408247 @default.
• W2298041512 cites W2030433731 @default.
• W2298041512 cites W2034942377 @default.
• W2298041512 cites W2039667151 @default.
• W2298041512 cites W2040005341 @default.
• W2298041512 cites W2045295833 @default.
• W2298041512 cites W2046078109 @default.
• W2298041512 cites W2046825058 @default.
• W2298041512 cites W2046878880 @default.
• W2298041512 cites W2050779639 @default.
• W2298041512 cites W2050818026 @default.
• W2298041512 cites W2052769401 @default.
• W2298041512 cites W2053162244 @default.
• W2298041512 cites W2056779425 @default.
• W2298041512 cites W2057769532 @default.
• W2298041512 cites W2059380840 @default.
• W2298041512 cites W2061144516 @default.
• W2298041512 cites W2066088601 @default.
• W2298041512 cites W2066632833 @default.
• W2298041512 cites W2067860210 @default.
• W2298041512 cites W2071760372 @default.
• W2298041512 cites W2072859071 @default.
• W2298041512 cites W2078043563 @default.
• W2298041512 cites W2078864507 @default.
• W2298041512 cites W2082747164 @default.
• W2298041512 cites W2083398163 @default.
• W2298041512 cites W2083696919 @default.
• W2298041512 cites W2087295915 @default.
• W2298041512 cites W2087298783 @default.
• W2298041512 cites W2088164258 @default.
• W2298041512 cites W2091910723 @default.
• W2298041512 cites W2092108176 @default.
• W2298041512 cites W2094591113 @default.
• W2298041512 cites W2095145098 @default.
• W2298041512 cites W2098034303 @default.
• W2298041512 cites W2100347281 @default.
• W2298041512 cites W2100796422 @default.
• W2298041512 cites W2113675798 @default.
• W2298041512 cites W2116528837 @default.
• W2298041512 cites W2126043496 @default.
• W2298041512 cites W2127886370 @default.
• W2298041512 cites W2129879061 @default.
• W2298041512 cites W2129894373 @default.
• W2298041512 cites W2137375645 @default.
• W2298041512 cites W2139936160 @default.
• W2298041512 cites W2140797130 @default.
• W2298041512 cites W2140883212 @default.
• W2298041512 cites W2147106126 @default.
• W2298041512 cites W2155053561 @default.
• W2298041512 cites W2160481768 @default.
• W2298041512 cites W2161857978 @default.
• W2298041512 cites W2163753548 @default.
• W2298041512 cites W2164361934 @default.
• W2298041512 cites W2168696636 @default.

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