4Q8D

Crystal structure of a macrocyclic beta-sheet peptide containing two beta-strands from amyloid beta residues 15-23

Summary for 4Q8D

• Entry DOI: 10.2210/pdb4q8d/pdb
• Descriptor: macrocyclic beta-sheet peptide incorporating residues amyloid beta 15-23, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total)
• Functional Keywords: beta-sheet, synthetic peptide, artificial macrocycle, de novo protein
• Total number of polymer chains: 2
• Total formula weight: 5037.19

Authors

Pham, J.D.,Spencer, R.K.,Chen, K.H.,Nowick, J.S. (deposition date: 2014-04-26, release date: 2014-08-13, Last modification date: 2023-11-15)

Primary citation

Pham, J.D.,Spencer, R.K.,Chen, K.H.,Nowick, J.S.
A Fibril-Like Assembly of Oligomers of a Peptide Derived from beta-Amyloid.
J.Am.Chem.Soc., 136:12682-12690, 2014

PubMed Abstract: A macrocyclic β-sheet peptide containing two nonapeptide segments based on Aβ(15-23) (QKLVFFAED) forms fibril-like assemblies of oligomers in the solid state. The X-ray crystallographic structure of macrocyclic β-sheet peptide 3 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 3 and homologues 4 and 5 form discrete tetramers, rather than extended fibril-like assemblies. The fibril-like assemblies of oligomers formed in the solid state by macrocyclic β-sheet 3 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.

PubMed: 25068693
DOI: 10.1021/ja505713y

Experimental method

X-RAY DIFFRACTION (1.746 Å)