Direct Observation of Nucleation and Growth in Amyloid Self-Assembly

摘要

The three-dimensional polypeptide ordering that occurs in proteinnfolding is initiated within early dynamic unfolded molten globulenintermediates.n1,2nWhile hydrophobic collapse driven backbonendesolvation is critical for nucleation and assembly of native proteinnstructure,n3nthe importance of these early steps in protein misfoldingnand the accompanying processes that lead to amyloid-based diseasesnare less well understood. Early kinetic models for amyloid assemblynposited that individual nucleating events create templates for thenaddition and conformational induction of new monomers.n4,5nParticle-like aggregates have also been detected early in assembly,n4,8ndocumented kinetically as on pathway,n6,7nand implicated in neuronalndysfunction.n9 12nThese results have led to various nucleatednconformational conversion modelsn13nwhich implicate intermediatendisordered oligomer assemblies as nucleation and propagationncenters.