%0 Journal Article
%A Gardon, Luis
%A Becker, Nina
%A Gremer, Lothar
%A Heise, Henrike
%T Structural Impact of N‐terminal Pyroglutamylate in an Amyloid‐β(3‐42) Fibril Probed by Solid‐State NMR Spectroscopy
%J Chemistry - a European journal
%V 30
%N 10
%@ 0947-6539
%C Weinheim
%I Wiley-VCH
%M FZJ-2024-00927
%P e202303007
%D 2024
%X Extracellular amyloid-β (Aβ) plaques, primarily formed by Aβ(1-40) and Aβ(1-42) fibrils, are a hallmark of Alzheimer's disease. The Aβ peptide can undergo a high variety of different post-translational modifications including formation of a pyroglutamate (pGlu, pE) at N-terminal Glu3 or Glu11 of truncated Aβ(3-x) or Aβ(11-x), respectively. Here we studied structural similarities and differences between pEAβ(3-42) and LS-shaped Aβ(1-42) fibrils grown under identical conditions (pH 2) using solid-state NMR spectroscopy. We show that the central region of pEAβ(3-42) fibrils including the turn region around V24 is almost identical to Aβ(1-42) showing similar β-strands also at the N-terminus. The missing N-terminal residues D1-A2 along with pE3 formation in pEAβ(3-42) preclude a salt bridge between K28-D1' as in Aβ(1-42) fibrils. G37 and G38 act as highly sensitive internal sensors for the modified N-terminus, which remains rigid over ~five pH units.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:001138572000001
%R 10.1002/chem.202303007
%U https://juser.fz-juelich.de/record/1021672