| Anne Gershenson
Associate Professor of Biochemistry and Molecular Biology, University of Massachusetts
Ph.D.: University of Michigan
Protein folding in the Endoplasmic Reticulum (ER)
In cells, proteins can fold vectorially (from the N to the C terminus) as they are being synthesized, and folding may be assisted by molecular chaperones. Protein folding in vivo is also complicated by the myriad of other macromolecules (>100 mg/ml) in the cell, reducing the space available to the folding protein resulting in many possible non-specific interactions. Thus, protein folding in the cell may be quite different than folding in the dilute solutions encountered in test tubes. In collaboration with Professors Lila Gierasch and Dan Hebert at the University of Massachusetts Amherst, we are extending our single molecule studies of secretory protein folding into the native folding environment, the endoplasmic reticulum.
Peripheral Membrane Proteins and Membrane Binding
Mammalian phospholipases are involved in a number of important signaling cascades, and some bacterial phospholipases are also virulence factors. Phospholipase function depends on transient interactions with target membranes, and we are particularly interested in how the affinity for membranes and the kinetics of binding depend on the lipid composition as well as how mutations affect membrane binding and activity. In collaboration with Professor Mary F. Roberts at Boston College we are using fluorescence correlation spectroscopy (FCS), a "small number of molecules" technique, as well as single molecule fluorescence microscopy to investigate how phospholipases interact with lipid membranes.
Gershenson A & Gierasch LM (2011) Protein folding in the cell: challenges and progress. Curr Opin Struct Biol 21: 32-41.
Pu, M., Roberts, M.F. & Gershenson, A. (2009) Fluorescence correlation spectroscopy of phosphatidylinositol-specific phospholipase C monitors the interplay of substrate and activator lipid binding. Biochemistry 48: 6835-6845.
Lu, L., Mushero, N., Hedstrom, L. & Gershenson, A. (2007) Short-lived protease serpin complexes: partial disruption of the rat trypsin active site. Protein Sci 16: 2403-2411.
Farbman, M.E., Gershenson, A. & Licht, S. (2007) Single-molecule analysis of nucleotide-dependent substrate binding by the protein unfoldase ClpA. J Am Chem Soc 129: 12378-12379.
Lu, L., Mushero, N., Hedstrom, L. & Gershenson, A. (2006) Conformational distributions of protease-serpin complexes: a partially translocated complex. Biochemistry 45: 10865-10872.