The Importance of Hydrogen Bonding between the Glutamine Side Chains to the Formation of Amyloid VQIVYK Parallel β-Sheets: An ONIOM DFT/AM1 Study

摘要

Amyloid fibrils formed from the tau protein are a symptom and probable cause of Alzheimer's disease. Mutation studies have shown that the six amino acid sequence ~(306)VQIVYK~(311) is essential for the formation of these fibrils.4'5 Recent crystallographic studies of VQIVYK peptides have shown that long needle-shaped crystals are formed from pairs of parallel β-sheets joined by a dry zipper-like structure formed from interdigitating side chains of adjacent β-strands, with the long axis of the needle perpendicular to the strands but parallel to the chains of amidic H-bonds that form the parallel β-sheets.