Structural Insights into Functional and Pathological Amyloid

Frank Shewmaker,Ryan P. McGlinchey,Reed B. Wickner

doi:10.1074/jbc.r111.227108

Abstract

Amyloid is traditionally viewed as a consequence of protein misfolding and aggregation and is most notorious for its association with debilitating and chronic human diseases. However, a growing list of examples of "functional amyloid" challenges this bad reputation and indicates that many organisms can employ the biophysical properties of amyloid for their benefit. Because of developments in the structural studies of amyloid, a clearer picture is emerging about what defines amyloid structure and the properties that unite functional and pathological amyloids. Here, we review various amyloids and place them within the framework of the latest structural models.

Highlights

Amyloid is traditionally viewed as a consequence of protein misfolding and aggregation and is most notorious for its association with debilitating and chronic human diseases
A protein structural view of amyloid began to emerge in the 1960s after the work of Cohen and Calkins [2], who first reported its non-branching fibrillar structure viewed by electron microscopy
How functional amyloid may be similar to or different from pathological amyloid is becoming clearer as more is learned about amyloid structure

Summary

Structural Insights into Functional and Pathological Amyloid*

Amyloid is a highly ordered protein aggregate with a filamentous morphology that is generally unbranched with indefinite length and diameters of ϳ2–20 nm. These fibrils are rich in ␤-sheet secondary structure and are formed by the noncovalent polymerization of a single protein with the polypeptide chains aligned in the cross-␤-configuration. Amyloid is generally relatively resistant to denaturation and proteolysis and shows yellow-green birefringence on binding Congo red and intense fluorescence on binding thioflavin T These dyes are imperfect reporters, and they are not necessarily specific to a single type of amyloid structure [6]. Several very different amyloid folds have been demonstrated, as outlined below

Challenges of Structure Elucidation

Homo sapiens

Amyloid Structure

Structural information

Amyloid Intermediate and Oligomeric Structures

Functional Versus Pathological Amyloid Structure

What Is Amyloid?