The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and ...

The diverse array of protein functions depends upon these molecules’ reliable ability to fold into the native structures determined by their amino-acid sequences. Because mutations that alter a protein’s sequence frequently disrupt its folding, protein evolution explores protein sequence space conservatively, either by point mutations or recombination between related sequences. Attempts to engi...

Diseases caused by protein misfolding are an emerging pathologic category that are thought to share some basic common mechanisms and display impressive heterogeneity in terms of tissue involvement, age of onset and clinical features. The growing recognition of the impact that protein misfolding has on human diseases is certainly related to the phenomenon of population aging and the expansion of...

Protein misfolding in the endoplasmic reticulum (ER) contributes to the pathogenesis of many diseases. Although oxidative stress can disrupt protein folding, how protein misfolding and oxidative stress impact each other has not been explored. We have analyzed expression of coagulation factor VIII (FVIII), the protein deficient in hemophilia A, to elucidate the relationship between protein misfo...

Over the past 25 years, enormous breakthroughs have been made in understanding protein folding mechanisms. We have now reached an exciting stage, with consensuses beginning to emerge that combine both theoretical and experimental approaches. In addition, new fields have emerged and burgeoned, including in vivo folding and the study of protein misfolding diseases. In today's post-genomic world, ...