Michael L. Gross, Ph.D.

Professor
Chemistry
Pathology and Immunology
Internal Medicine

Biochemistry, Biophysics, and Structural Biology Program

  • 314-935-4814

  • 314-935-7485

  • 314-935-7484

  • 1134

  • 101 Cyclotron Building

  • mgross@wustl.edu

  • http://msr.dom.wustl.edu/

  • amyloid beta biophysics, biochemistry, biophysics, mass spectrometry, protein-protein interaction, protein structure,

  • Development and application of mass spectrometry in biophysics, biochemistry, and medicine

Research Abstract:

Our principal research goal is to develop mass spectrometry (MS) instrumentation and methods for protein biophysics and structural proteomics. We wish to understand protein folding, to determine ligand binding sites, to quantify protein/ligand interactions, and to determine protein interfaces especially for systems involved in protein misfolding. Our goal is a "tool box" of various methods involving covalent footprinting of proteins (e.g., H/D amide exchange, reactive radical footprinting, and specific chemical reactions). We currently emphasize H/D exchange of proteins, as monitored by ESI, as an approach to understanding protein folding and interactions. We extended this by building a new method (PLIMSTEX) in which we use exchange and modeling to determine protein/ligand interactions. We also are investigating the reactions of OH and other radicals, generated with a short laser pulse, with proteins as a structural tool that is complementary to H/D exchange . We seek to discover new reactions for protein footprinting and to test applicability in problem solving. The instrumentation we use for this research are a Quadrupole/Time-of-Flight mass spectrometer, a 12-tesla FT-Ion Cyclotron Resonance mass spectrometer, an Orbitrap, and two 7-tesla FT ICR mass spectrometers. Analysis is by both "bottom-up" and "top-down" MS-based proteomics utilizing electrospray ionization, native spray, and high resolving power mass analyzers. We are also interested in developing Fourier transform mass spectrometry by implementing new ion-trapping methods and electrically compensated cells to afford improvements in mass resolving power, mass measurement, and ability to store, manipulate, and react biomolecule ions and reactive species. Our laboratory is also a NIH research resource commissioned to provide collaboration and service in mass spectrometry including molecular weight measurement, accurate mass measurement, tandem mass spectrometry experiments, and proteomics. We seek collaborations particularly in the area of biophysical properties of proteins and top-down protein sequencing.

Selected Publications:

Gau BC, Chen J, and Gross ML.(2013). Fast Photochemical Oxidation of Proteins for Comparing Solvent-Accessibility Changes Accompanying Protein Folding: Data Processing and Application to Barstar, Biochem. Biophys. Acta, 1834:1230-1238. PMCID:PMC3663899

Liu H, Chen J, Huang, RYC., Weisz D, Gross ML, Pakrasi HB. (2013) Mass spectrometry-based footprinting reveals structural dynamics of loop e of the chlorophyll-binding protein CP43 during photosystem II assembly in the cyanobacterium synechocystis 6803. J. Biol. Chem., 288: 14212-14220. PMCID:PMC3656277

Jones LM, Zhang & Gross ML. (2013). Complementary MS Methods Assist Conformational Characterization of Antibodies with Altered S-S Bonding Networks, (2013). J. Am. Soc. Mass Spectrom., 24:835-845. PMCID:PMC3651811

Zhang J, Luo M, Marasco D, Logsdon D, Lafavers KA, Chen Q, Reed A, Kelley MR, Gross ML, & Georgiadis MM. (2013). Inhibition of Apurinic/apyrimidinic Endonuclease I`s Redox Activity Revisited, Biochemistry, 52:2955-2966. PMCID:PMC3706204

Chen J, Rempel DL, Gau BC, & Gross ML. (2012) Fast Photochemical Oxidation of Proteins (FPOP) and Mass Spectrometry Follow Sub-millisecond Protein Folding at the Amino-Acid Level, J. Am. Chem. Soc., 134:18724–18731. PMCID:PMC3498593

Chen J, Cui W, Giblin D, Gross ML. (2012) New Protein Footprinting: Fast Photochemical Iodination Combined with Top-Down and Bottom-Up Mass Spectrometry, J. Am. Soc. Mass Spectrom., 23:1306-1318. PMCID:PMC3630512

Huang RYC, Wen J, Blankenship RE, & Gross ML.(2012). Hydrogen–Deuterium Exchange Mass Spectrometry Reveals the Interaction of Fenna–Matthews–Olson Protein and Chlorosome CsmA Protein, Biochemistry, 51:187-193. PMCID:PMC3254703

Huang RY, Garai K, Frieden C, Gross ML. Hydrogen/Deuterium exchange and electron-transfer dissociation mass spectrometry determine the interface and dynamics of apolipoprotein E oligomerization.Biochemistry 2011 50(43):9273-82. PMID:21899263

Gau B, Garai K, Frieden C, Gross ML (2011). Mass spectrometry-based protein footprinting characterizes the structures of oligomeric apolipoprotein E2, E3, and E4,Biochemistry, 50(38):8117-26. PMID: 21848287.

Huang RY, Rempel DL, Gross ML. HD exchange and PLIMSTEX determine the affinities and order of binding of Ca2+ with troponin C. Biochemistry 2011 50(24):5426-35. PMID:21574565

Last Updated: 7/30/2013 10:13:11 AM

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