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

作者：Wei Juan; Antzutkin Oleg N; Filippov Andrei V; Iuga Dinu; Lam Pui Yiu; Barrow Mark P; Dupree Ray; Brown Steven P; O'Connor Peter B^*

来源：Biochemistry, 2016, 55(14): 2065-2068.

DOI：10.1021/acs.biochem.5b01095

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 A beta species in forming hydrogen -bonded networks. Two Alzheimer's A beta peptides, Ac-A beta(16-22)-NH2 and A beta(11-25), selectively labeled with O-17 and N-15 at specific amino acid residues were investigated. The total amount of peptides labeled with O-17 as measured by FTICR-MS enabled the interpretation of dephasing observed in N-15{O-17}-REAPDOR solid-state NMR experiments. Specifically, about one-third of the A beta peptides were found to be involved in the formation of a specific >C=O-17 center dot center dot center dot H-N-15 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.

• 出版日期2016-4-12