Proteins perform vital cellular functions; however, in order to work, these chain-like molecules must fold into complex, three-dimensional structures1 (Fig.1). The process is quality controlled by complex molecules within the cell2,3; however, it can go awry, yielding misfolded proteins that clump into toxic aggregates (Fig. 2). Many age-related diseases, such as Alzheimer’s disease, are thought to be caused by the build-up of these aggregates4,5. A co-ordinated network of interdisciplinary research is developing therapies that aim to remove or prevent the build-up of these misfolded proteins. If successful, their potential to improve quality of life is immense.
Proteins are the workhorses of the cell: they are essential molecules that fulfil vital and diverse cellular functions, such as catalysing chemical reactions, providing structural support, and mediating cell signalling and development. Human cells contain thousands of proteins, each consisting of a chain of 100–500 amino-acid building blocks. In order to work, however, these newly built proteins must first fold into a complex yet highly specific three-dimensional shape.
With hundreds of thousands of different possible structures for each protein, achieving the correct one is a tall order; yet, most proteins manage to perform this task quickly and efficiently. Larger proteins tackle the problem by folding different parts of the molecule separately. The process is driven by hydrophobic and hydrophilic properties of amino acids in different sections of the protein. Water-repelling amino acids interact with one other to build a hydrophobic core, whereas water-attracting amino acids settle on the exterior of the protein. This causes the protein chain to collapse into a globular structure that forms a stable, three-dimensional, biologically active protein.