Taking charge of proteins from neurodegeneration to industrial biotechnology.

The aggregation and precipitation of a soluble protein-within a motor neuron, or a pharmaceutical vial, or even inside a industrial-scale hydrolysis chamber-is a problem in human health and in biotechnology. A growing body of research is suggesting that the magnitude of the net charge of a protein is a determinant of the rate at which proteins self-assemble in solution into aggregates with amorphous or fibrillar (or uncharacterized) morphologies. This chapter discusses how this apparently simple electrostatic effect might explain-in part or entirely-the pathogenicity of some mutations that cause familial protein aggregation diseases-especially the familial forms of amyotrophic lateral sclerosis that are caused by mutations in the gene encoding superoxide dismutase-1 (SOD1). In parallel, this chapter also discusses how understanding these electrostatic effects can guide the engineering of industrial enzymes (such as alpha-amylase from Bacillus licheniformis) into forms that are more resistant to aggregation and thermal precipitation than the enzymes that are currently used, for example, in the production of ethanol from starch or cellulose.