Amyloid beta-protein: experiment and theory on the 21-30 fragment.
The structure of the 21-30 fragment of the amyloid beta-protein (Abeta) was investigated by ion mobility mass spectrometry and replica exchange dynamics simulations. Mutations associated with familial Alzheimer's disease (E22G, E22Q, E22K, and D23N) of Abeta(21-30) were also studied, in order to understand any structural changes that might occur with these substitutions. The structure of the WT peptide shows a bend and a perpendicular turn in the backbone which is maintained by a network of D23 hydrogen bonding. Results for the mutants show that substitutions at E22 do little to alter the overall structure of the fragment. A substitution at D23 resulted in a change of structure for Abeta(21-30). A comparison of these gas-phase studies to previous solution-phase studies reveals that the peptide can fold in the absence of solvent to a structure also seen in solution, highlighting the important role of the D23 hydrogen bonding network in stabilizing the fragment's folded structure.
Murray
Megan M
MM
Department of Chemistry, University of California, Santa Barbara, California 93106, USA.
Krone
Mary Griffin
MG
Bernstein
Summer L
SL
Baumketner
Andrij
A
Condron
Margaret M
MM
Lazo
Noel D
ND
Teplow
David B
DB
Wyttenbach
Thomas
T
Shea
Joan-Emma
JE
Bowers
Michael T
MT