Peptide segment GNNQQNY from Sup35 forming amyloid-like fibrils
Saccharomyces cerevisiae (Baker's yeast)
Amyloid is an insoluble fibrous protein found in body, and is not usually over-expressed since the amount of synthesis and degradation are usually same. In the brain of Alzheimer's disease (AD) patient’s brain, “senile plaques” consisting of amyloid fibrils are observed and it is suggested that the decrease in amyloid degrading ability induces amyloid accumulation and causes AD. Bovine sponge-form encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD), transmissible sponge-form encephalopathy (TSE) and so on are similar prion diseases. Though amyloid-like fibrils may be formed from normally functioning proteins, there is no common structure of such proteins in normal state. But amyloid-like fibrils have the so-called cross beta sheet structure. One of the proteins which are known to form amyloid fibrils is the Sup35 protein from yeast. Normally this protein works as a translation terminating factor, but the conversion of the N-terminal domain to the amyloid-like fibrils causes a transmissible infection akin to mammalian prions The structure shown here is a seven-residue peptide segment GNNQQNY, derived from the part which may change it's structure.
This molecule stacks in register in parallel, forms hydrogen bond with adjacent molecules, and beta sheets. A beta sheet faces another beta sheet in antiparallel, then the inner sides of two sheets form "dry" interfaces without water molecules, and the opposite sides form "wet" interfaces which include water. These opposing side chains complement each other closely, forming van der Waals interactions. These pairs of sheets are likely to be a fundamental feature of amyloid-like fibrils.
Protein Data Bank (PDB)
author: Takahiro Kudou