Research in our laboratory aims at understanding the structural biology of molecular chaperones in folding and translocation of polypeptides as they emerge from the ribosome and are released into the cytosol. Cellular synthesis of polypeptides is an amazing, complex, and efficient process. Each newly synthesized protein, however, must be folded into its correct tertiary structure and transported to the correct cellular location for proper function. How this is achieved remains to be one of the most challenging questions in molecular biology. In addition, improper folding and translocation of proteins have been directly implicated in many disease states. Molecular chaperones were initially identified as proteins that can facilitate the refolding of proteins denatured in the cytosol due to heat or chemical stress. Their functions to assist protein folding largely derive from their abilities to bind and stabilize hydrophobic segments exposed in protein non-native conformation. Work in the past decade demonstrated that molecular chaperones play even bigger roles under non-stress conditions. They ensure that newly synthesized polypeptides are properly folded into their active forms and transported to their intended cellular destinations. Research in our laboratory integrates the tools of X-ray crystallography, protein biochemistry and molecular biology into a program of analysis of the role of molecular chaperones in cellular protein folding and translocation. By revealing the three-dimensional structures of molecular chaperones and their complexes with peptides and with various upstream or downstream partners, we will gain insight into the key mechanisms used by these important molecules. Such information can be used to explain the roles of these proteins in ensuring a healthy growing cell, and will lead us towards a coherent molecular understanding about how newly synthesized proteins are folded into their correct tertiary structures and transported to the correct cellular locations for proper function.