10.1021/bi036248t.s001
Waltteri Hosia
Waltteri
Hosia
Niklas Bark
Niklas
Bark
Edvards Liepinsh
Edvards
Liepinsh
Agneta Tjernberg
Agneta
Tjernberg
Bengt Persson
Bengt
Persson
Dan Hallén
Dan
Hallén
Johan Thyberg
Johan
Thyberg
Jan Johansson
Jan
Johansson
Lars Tjernberg
Lars
Tjernberg
Folding into a β-Hairpin Can Prevent Amyloid Fibril Formation<sup>†</sup>
American Chemical Society
2004
size exclusion chromatography
motif
form fibrils
sequence
electrospray mass spectrometry
polymerization
dodecapeptide KFFEYNGKKFFE
modeling studies
fibril formation
tetrapeptide KFFE
KFFE tetrapeptides
NMR spectroscopy
amyloidogenic properties
dodecapeptide KFFEAAAKKFFE forms
fibril bundles
sedimentation analysis
2004-04-27 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Folding_into_a_Hairpin_Can_Prevent_Amyloid_Fibril_Formation_sup_sup_/3341671
The tetrapeptide KFFE is one of the shortest amyloid fibril-forming peptides described. Herein,
we have investigated how the structural environment of this motif affects polymerization. Using a turn
motif (YNGK) or a less rigid sequence (AAAK) to fuse two KFFE tetrapeptides, we show by several
biophysical methods that the amyloidogenic properties are strongly dependent on the structural environment.
The dodecapeptide KFFEAAAKKFFE forms abundant thick fibril bundles. Freshly dissolved
KFFEAAAKKFFE is monomeric and shows mainly disordered secondary structure, as evidenced by circular
dichroism, NMR spectroscopy, hydrogen/deuterium exchange measurements, and molecular modeling
studies. In sharp contrast, the dodecapeptide KFFEYNGKKFFE does not form fibrils but folds into a
stable β-hairpin. This structure can oligomerize into a stable 12-mer and multiples thereof, as shown by
size exclusion chromatography, sedimentation analysis, and electrospray mass spectrometry. These data
indicate that the structural context in which a potential fibril forming sequence is present can prevent
fibril formation by favoring self-limiting oligomerization over polymerization.