title: Dynamic behavior of small heat shock protein inhibition on amyloid fibrillization of a small peptide (SSTSAA) from RNase A.
abstract: Small heat shock proteins, a class of molecular chaperones, are reported to inhibit amyloid fibril formation in vitro, while the mechanism of inhibition remains unknown. In the present study, we investigated the mechanism by which Mj HSP16.5 inhibits amyloid fibril formation of a small peptide (SSTSAA) from RNase A. A model peptide (dansyl-SSTSAA-W) was designed by introducing a pair of fluorescence resonance energy transfer (FRET) probes into the peptide, allowing for the monitoring of fibril formation by this experimental model. Mj HSP16.5 completely inhibited fibril formation of the model peptide at a molar ratio of 1:120. The dynamic process of fibril formation, revealed by FRET, circular dichroism, and electron microscopy, showed a lag phase of about 2 h followed by a fast growth period. The effect of Mj HSP16.5 on amyloid fibril formation was investigated by adding it into the incubation solution during different growth phases. Adding Mj HSP16.5 to the incubating peptide before or during the lag phase completely inhibited fibril formation. However, introducing Mj HSP16.5 after the lag phase only slowed down the fibril formation process by adhering to the already formed fibrils. These findings provide insight into the inhibitory roles of small heat shock proteins on amyloid fibril formation at the molecular level.
authors.affiliation: BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xi
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Luhua
authors.initials: L
authors.lastname: Lai
mesh_terms: D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D019843:Archaeal Proteins / Q000494:pharmacology*; D002942:Circular Dichroism; D031541:Fluorescence Resonance Energy Transfer; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D008854:Microscopy, Electron; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000737:chemistry; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D000682:Amyloid; D019843:Archaeal Proteins; C113795:HSP16.5 protein, Methanococcus jannaschii; D006360:Heat-Shock Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; C569515:SSTSAA peptide; D012259:Ribonuclease, Pancreatic