The University of Massachusetts Amherst
 
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Anne Gershenson

Associate Research Professor

Research areas include protein folding, protein-membrane interactions, single molecule fluorescence microscopy, fluorescence correlation spectroscopy.

Current Research
Research in my group focuses on protein folding and protein-membrane interactions using single molecule fluorescence microscopy and fluorescence correlation spectroscopy. One major goal is to connect protein folding in simple test tube systems to protein folding in the more complicated cellular environment with a particular emphasis on the serpin family of protease inhibitors, which easily misfold. For protein-membrane interactions, we are studying how virulence-associated peripheral membrane enzymes from Gram-positive bacteria recognize host membranes.  In collaboration with Prof. Li-Jun Ma my lab is also investigating interactions between proteins
(effectors) secreted by fungi and plant cells.

Inhibitory serpins regulate proteases involved in important physiological processes including inflammation, blood coagulation and blood clot clearance. Serpins use a mousetrap mechanism to mechanically deform and thus inhibit target proteases, but this conformational lability may enhance the probability of disease-associated misfolding and aggregation. We are using single molecule fluorescence techniques guided by new computational methods to monitor the conformational distributions of folding serpins in the test tube and are working on applying these techniques to more complicated systems such as serpin folding isolated endoplasmic reticula (microsomes) and cells. Our results will help elucidate how these metastable, conformationally labile proteins fold, how cells modulate serpin folding and why some disease associated serpin mutants aggregate in the endoplasmic reticulum.

Secreted phosphatidylinositol-specific phospholipase Cs (PI-PLCs) can enhance bacterial virulence, apparently by down-regulating host innate immunity. PI-PLCs from Bacillus species and Staphylococcus aureus target the outer leaflet of host cell membranes. Despite structural and sequence similarities, we and our collaborators have shown that these PI-PLCs use different membrane binding strategies. Bacillus PI-PLC specifically binds to phosphatidylcholine (PC) using cation-π interactions between the choline headgroup and PI-PLC Tyr residues, and this PC-specific binding motif may be used by other proteins. By contrast, Staphylococcus PI-PLC membrane binding is not PC specific but is enhanced by dimerization and acidic pHs. Listeria monocytogenes PI-PLC is secreted inside host cells and electrostatic interactions appear to make a large contribution to membrane recognition. By combining a variety of biophysical, biochemical and computational methods, we have elucidated how different environmental niches may modulate membrane recognition by homologous enzymes. These methods can easily be applied to a variety of peripheral membrane proteins.

Learn more at www.biochem.umass.edu/faculty/anne-gershenson

Academic Background

  • AB Bryn Mawr College, 1990
  • PhD University of Michigan Ann Arbor, 1996
  • Postdoctoral Training: California Institute of Technology, 1997-2000; University of Illinois Urbana-Champaign, 2000-2001
Roberts, M.F., Khan, H.M., Goldstein, R., Reuter, N. & Gershenson, A. (2018, in press) Search and subvert: Minimalist bacterial phosphatidylinositol-specific phospholipase (PI-PLC) enzymes. Chem Rev
Wang F., Orioli S., Ianeselli A., Spagnolli G., a Beccara S., Gershenson A., Faccioli P., Wintrode P.L. (2018) All-atom simulations reveal how single point mutations promote serpin misfolding. Biophys J 114: 2083–2094.
Chandrasekhar, K., Ke, H., Wang, N., Goodwin, T., Gierasch, L.M., Gershenson, A. & Hebert, D.N. (2016) Cellular folding of a metastable serpin. Proc Natl Acad Sci USA 113: 6484-6489.
Yang, B., Pu, M., Khan, H.M., Friedman, L.J., Reuter, N., Roberts, M.F. & Gershenson, A. (2015) Quantifying transient interactions between Bacillus phosphatidylinositol-specific phospholipase-C and phosphatidylcholine-rich vesicles. J Am Chem Soc 137: 14-17.
Gershenson, A., Gierasch, L.M., Pastore, A. & Radford, S.E. (2014) Energy landscapes of functional proteins are inherently risky. Nat Chem Biol 10: 884-891.
 
Contact Info

Department Biochemistry and Molecular Biology
N33 Life Sciences Laboratory
240 Thatcher Way
Amherst, MA 01003-9292

(413) 545-1250
gershenson@biochem.umass.edu

www.biochem.umass.edu/faculty/anne-gershenson