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@ARTICLE{Gardon:1021672,
author = {Gardon, Luis and Becker, Nina and Gremer, Lothar and Heise,
Henrike},
title = {{S}tructural {I}mpact of {N}‐terminal {P}yroglutamylate
in an {A}myloid‐β(3‐42) {F}ibril {P}robed by
{S}olid‐{S}tate {NMR} {S}pectroscopy},
journal = {Chemistry - a European journal},
volume = {30},
number = {10},
issn = {0947-6539},
address = {Weinheim},
publisher = {Wiley-VCH},
reportid = {FZJ-2024-00927},
pages = {e202303007},
year = {2024},
abstract = {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.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
UT = {WOS:001138572000001},
doi = {10.1002/chem.202303007},
url = {https://juser.fz-juelich.de/record/1021672},
}