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• W2000659036 endingPage "1596" @default.
• W2000659036 startingPage "1581" @default.
• W2000659036 abstract "Neurotoxic assemblies of the amyloid beta-protein (Abeta) have been linked strongly to the pathogenesis of Alzheimer's disease (AD). Here, we sought to monitor the earliest step in Abeta assembly, the creation of a folding nucleus, from which oligomeric and fibrillar assemblies emanate. To do so, limited proteolysis/mass spectrometry was used to identify protease-resistant segments within monomeric Abeta(1-40) and Abeta(1-42). The results revealed a 10-residue, protease-resistant segment, Ala21-Ala30, in both peptides. Remarkably, the homologous decapeptide, Abeta(21-30), displayed identical protease resistance, making it amenable to detailed structural study using solution-state NMR. Structure calculations revealed a turn formed by residues Val24-Lys28. Three factors contribute to the stability of the turn, the intrinsic propensities of the Val-Gly-Ser-Asn and Gly-Ser-Asn-Lys sequences to form a beta-turn, long-range Coulombic interactions between Lys28 and either Glu22 or Asp23, and hydrophobic interaction between the isopropyl and butyl side chains of Val24 and Lys28, respectively. We postulate that turn formation within the Val24-Lys28 region of Abeta nucleates the intramolecular folding of Abeta monomer, and from this step, subsequent assembly proceeds. This model provides a mechanistic basis for the pathologic effects of amino acid substitutions at Glu22 and Asp23 that are linked to familial forms of AD or cerebral amyloid angiopathy. Our studies also revealed that common C-terminal peptide segments within Abeta(1-40) and Abeta(1-42) have distinct structures, an observation of relevance for understanding the strong disease association of increased Abeta(1-42) production. Our results suggest that therapeutic approaches targeting the Val24-Lys28 turn or the Abeta(1-42)-specific C-terminal fold may hold promise." @default.
• W2000659036 created "2016-06-24" @default.
• W2000659036 creator A5007792240 @default.
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• W2000659036 creator A5047907332 @default.
• W2000659036 creator A5052624773 @default.
• W2000659036 creator A5057183403 @default.
• W2000659036 date "2009-01-01" @default.
• W2000659036 modified "2023-10-07" @default.
• W2000659036 title "On the nucleation of amyloid β-protein monomer folding" @default.
• W2000659036 cites W112323419 @default.
• W2000659036 cites W1516306407 @default.
• W2000659036 cites W1518693759 @default.
• W2000659036 cites W1552345552 @default.
• W2000659036 cites W1584774790 @default.
• W2000659036 cites W1648265574 @default.
• W2000659036 cites W165011375 @default.
• W2000659036 cites W1677883125 @default.
• W2000659036 cites W1964991231 @default.
• W2000659036 cites W1965895512 @default.
• W2000659036 cites W1966596430 @default.
• W2000659036 cites W1969165181 @default.
• W2000659036 cites W1970435618 @default.
• W2000659036 cites W1972535964 @default.
• W2000659036 cites W1972567838 @default.
• W2000659036 cites W1974130870 @default.
• W2000659036 cites W1976210162 @default.
• W2000659036 cites W1977761007 @default.
• W2000659036 cites W1979543098 @default.
• W2000659036 cites W1981735680 @default.
• W2000659036 cites W1985469117 @default.
• W2000659036 cites W1987426556 @default.
• W2000659036 cites W1989270637 @default.
• W2000659036 cites W1991388423 @default.
• W2000659036 cites W1995175521 @default.
• W2000659036 cites W1996837502 @default.
• W2000659036 cites W2001250831 @default.
• W2000659036 cites W2001318407 @default.
• W2000659036 cites W2001928135 @default.
• W2000659036 cites W2002911779 @default.
• W2000659036 cites W2005848422 @default.
• W2000659036 cites W2006548790 @default.
• W2000659036 cites W2006765669 @default.
• W2000659036 cites W2008824844 @default.
• W2000659036 cites W2012561243 @default.
• W2000659036 cites W2014451295 @default.
• W2000659036 cites W2021417643 @default.
• W2000659036 cites W2024559246 @default.
• W2000659036 cites W2026684847 @default.
• W2000659036 cites W2029018340 @default.
• W2000659036 cites W2029695041 @default.
• W2000659036 cites W2032665239 @default.
• W2000659036 cites W2033382511 @default.
• W2000659036 cites W2033847972 @default.
• W2000659036 cites W2041851607 @default.
• W2000659036 cites W2042742422 @default.
• W2000659036 cites W2044862505 @default.
• W2000659036 cites W2045287375 @default.
• W2000659036 cites W2046974636 @default.
• W2000659036 cites W2051651977 @default.
• W2000659036 cites W2052417023 @default.
• W2000659036 cites W2053354342 @default.
• W2000659036 cites W2054561210 @default.
• W2000659036 cites W2055805017 @default.
• W2000659036 cites W2056449014 @default.
• W2000659036 cites W2059392350 @default.
• W2000659036 cites W2063272219 @default.
• W2000659036 cites W2064626179 @default.
• W2000659036 cites W2067214887 @default.
• W2000659036 cites W2067362253 @default.
• W2000659036 cites W2067814874 @default.
• W2000659036 cites W2073394015 @default.
• W2000659036 cites W2073516240 @default.
• W2000659036 cites W2074655761 @default.
• W2000659036 cites W2075243013 @default.
• W2000659036 cites W2076453964 @default.
• W2000659036 cites W2076834744 @default.
• W2000659036 cites W2079492580 @default.
• W2000659036 cites W2084513527 @default.
• W2000659036 cites W2084972185 @default.
• W2000659036 cites W2086278983 @default.
• W2000659036 cites W2087082736 @default.
• W2000659036 cites W2091369493 @default.
• W2000659036 cites W2093653062 @default.
• W2000659036 cites W2093942461 @default.
• W2000659036 cites W2099653907 @default.
• W2000659036 cites W2111766718 @default.
• W2000659036 cites W2112226950 @default.
• W2000659036 cites W2114078421 @default.
• W2000659036 cites W2114320763 @default.
• W2000659036 cites W2118241214 @default.
• W2000659036 cites W2124929769 @default.
• W2000659036 cites W2130137989 @default.
• W2000659036 cites W2132220200 @default.
• W2000659036 cites W2134293050 @default.
• W2000659036 cites W2140393791 @default.
• W2000659036 cites W2146610745 @default.
• W2000659036 cites W2150999725 @default.

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