Converging concepts of protein folding in vitro and in vivo

Most proteins must fold into precise three-dimensional conformations to fulfill their biological functions. Here we review recent concepts emerging from studies of protein folding in vitro and in vivo, with a focus on how proteins navigate the complex folding energy landscape inside cells with the aid of molecular chaperones. Understanding these reactions is also of considerable medical relevance, as the aggregation of misfolding proteins that escape the cellular quality-control machinery underlies a range of debilitating diseases, including many age-onset neurodegenerative disorders.