Amyloid Hydrogen Bonding Polymorphism Evaluated by 15N{17O}REAPDOR Solid-State NMR and Ultra-High Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

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• 作者：Juan Wei ; Oleg N. Antzutkin ; Andrei V. Filippov ; Dinu Iuga ; Pui Yiu Lam ; Mark P. Barrow ; Ray Dupree ; Steven P. Brown ; Peter B. O’Connor
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：April 12, 2016
• 年：2016
• 卷：55
• 期：14
• 页码：2065-2068
• 全文大小：335K
• 年卷期：0
• ISSN：1520-4995

文摘

A combined approach, using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and solid-state NMR (Nuclear Magnetic Resonance), shows a high degree of polymorphism exhibited by Aβ species in forming hydrogen-bonded networks. Two Alzheimer’s Aβ peptides, Ac-Aβ_16–22-NH₂ and Aβ_11–25, selectively labeled with ¹⁷O and ¹⁵N at specific amino acid residues were investigated. The total amount of peptides labeled with ¹⁷O as measured by FTICR-MS enabled the interpretation of dephasing observed in ¹⁵N{¹⁷O}REAPDOR solid-state NMR experiments. Specifically, about one-third of the Aβ peptides were found to be involved in the formation of a specific >C═¹⁷O···H–¹⁵N hydrogen bond with their neighbor peptide molecules, and we hypothesize that the rest of the molecules undergo ± n off-registry shifts in their hydrogen bonding networks.