Elizabeth Anne Craig

Proteins must fold into their native active conformations to function properly within the cell. Molecular chaperones are a highly conserved group of proteins that facilitate the folding of other proteins as well as their translocation across membranes by transiently binding to their unfolded forms. Utilizing the yeast Saccharomyces cerevisiae as a model organism, my laboratory has analyzed the family of molecular chaperones of the Hsp70 (Heat Shock Protein 70) class to understand their complex roles in these central cellular processes. We are focusing on two cellular processes in which these chaperones play a crucial role: the early stages of protein synthesis and protein translocation into mitochondria. During their synthesis on ribosomes, proteins are particularly susceptible to aggregation, which prohibits their proper folding. An Hsp70 molecular chaperone is one of the first proteins to interact with nascent chains on the ribosome. Secondly, during the process of translocation of proteins across the inner membrane of mitochondria, Hsp70 binds to polypeptides, traversing the membrane, facilitating their movement into the mitochondrial matrix. Understanding the molecular mechanism by which chaperones act in these processes with the assistance of cochaperones and other interacting proteins is crucial to an understanding of how proteins fold within cells.