To a first approximation, a protein's sequence determines its fold, and its fold determines its function. However, many proteins require post-translational modifications, trafficking to the proper location in the cell, or incorporation into multi-protein architectures before they can function. We study the structures and mechanisms of enzymes and other factors involved in modification, localization, and assembly of proteins.
Driven by the fascination of exploring at atomic level the macromolecules involved in complex cellular processes, the technique of X-ray crystallography is the foundation of the laboratory. We combine crystallography with proteomics, microscopy, various spectroscopies, and other approaches to answer, as thoroughly as possible, the mechanistic and functional questions that arise from our structures.
We currently focus on the mechanism by which proteins are enzymatically cross-linked with disulfide bonds upon entry into the endoplasmic reticulum or Golgi apparatus, or upon export from the cell. We are also exploring the physiological roles of disulfide catalysts that function downstream of the endoplasmic reticulum. Furthermore, since reactive oxygen species can be formed as a byproduct of disulfide formation, we are also interested in potential negative effects of disulfide catalysts on sensitive cells, such as neurons under stress.