Folding and wrapping soluble proteins: Exploring the molecular basis of cooperativity and aggregation

ARIEL FERNANDEZ; XI ZHANG; JIANPING CHEN

Progress in Molecular Biology and Translational Science 83, 53-88 (2008)

Academic Press

Año: 2008; p. 53 - 88

In this chapter, we survey recent advances in the understanding of the folding of soluble proteins, mostly focusing on the molecular basis of cooperativity. In this regard, we explore the concept of protein wrapping and its bearing on the expediency of the folding process for natural proteins. Wrapping refers to the environmental modulation or protection of intramolecular electrostatic interactions through an exclusion of surrounding water that takes place as the chain folds onto itself. Thus, a special many‐body picture of the folding process is shown to emerge where the folding chain not only interacts with itself but also shapes the microenvironments that stabilize or destabilize the interactions. After describing reported results on the dynamics of folding, wrapping and water exclusion, we examine the endpoint of the folding process. In particular, we classify folds according to their extent of wrapping and explore relationships between severely under‐wrapped proteins, aggregation, and epigenetic polymorphism.