A Fibril-Like Assembly of Oligomers of a Peptide Derived from β‑Amyloid
Johnny
D. Pham
Ryan K. Spencer
Kevin H. Chen
James S. Nowick
10.1021/ja505713y.s004
https://acs.figshare.com/articles/dataset/A_Fibril_Like_Assembly_of_Oligomers_of_a_Peptide_Derived_from_Amyloid/2039598
A macrocyclic
β-sheet peptide containing two nonapeptide
segments based on Aβ<sub>15–23</sub> (QKLVFFAED) forms
fibril-like assemblies of oligomers in the solid state. The X-ray
crystallographic structure of macrocyclic β-sheet peptide <b>3</b> was determined at 1.75 Å resolution. The macrocycle
forms hydrogen-bonded dimers, which further assemble along the fibril
axis in a fashion resembling a herringbone pattern. The extended β-sheet
comprising the dimers is laminated against a second layer of dimers
through hydrophobic interactions to form a fibril-like assembly that
runs the length of the crystal lattice. The second layer is offset
by one monomer subunit, so that the fibril-like assembly is composed
of partially overlapping dimers, rather than discrete tetramers. In
aqueous solution, macrocyclic β-sheet <b>3</b> and homologues <b>4</b> and <b>5</b> form discrete tetramers, rather than
extended fibril-like assemblies. The fibril-like assemblies of oligomers
formed in the solid state by macrocyclic β-sheet <b>3</b> represent a new mode of supramolecular assembly not previously observed
for the amyloidogenic central region of Aβ. The structures observed
at atomic resolution for this peptide model system may offer insights
into the structures of oligomers and oligomer assemblies formed by
full-length Aβ and may provide a window into the propagation
and replication of amyloid oligomers.
2015-12-17 04:20:12
Peptide Derived
homologues 4
5 form
nonapeptide segments
supramolecular assembly
monomer subunit
oligomer assemblies
QKLVFFAED
herringbone pattern
crystal lattice
fibril axis
macrocyclic
amyloid oligomers
dimers
peptide model system
1.75 Å resolution