Intrinsic conformational preference in the monomeric protein governs amyloid polymorphism.

The inherent stochasticity associated with the hierarchical self-assembly of either native-like or partially-unfolded protein monomers leads to the formation of transient, morphologically-diverse prefibrillar species resulting in structurally-distinct polymorphic protein aggregates. High-resolution structural characterization of mature aggregates has revealed heterogeneous supramolecular packing of protofibrils within amyloid polymorphs. However, little is known about whether initial monomeric protein conformers engender polymorphism at the onset of aggregation.

The protein-surfactant stoichiometry governs the conformational switching and amyloid nucleation kinetics of tau K18.

Amyloids are pathological hallmarks of a number of debilitating neurodegenerative diseases. Understanding the molecular mechanism of protein amyloid assembly with an emphasis on structural characterization of early, key prefibrillar species is important for targeted drug design and clinical interventions. Tau is an intrinsically disordered, microtubule-binding protein which is also implicated in various neurodegenerative disorders such as frontotemporal dementia, Down's syndrome, Alzheimer's disease, etc.