Brian F. Volkman, Ph.D.
Associate Professor
Dr. Volkman obtained his Bachelor of Science degree in Chemistry and Physics from Butler University in 1989 and his Doctorate degree from The University of California at Berkeley. The latter was awarded in 1994 for structural studies on proteins involved in bacterial gene regulation using NMR spectroscopy. Dr. Volkman's postdoctoral training was in the Department of Biochemistry at the University of Wisconsin-Madison. In 2000, Dr. Volkman started at the Medical College of Wisconsin where he is Associate Professor in the Biochemistry Department. Dr. Volkman's work focuses on the structural biology of immunological signalling molecules and the use of NMR spectroscopy in structural proteomics.
Contact Information
bvolkman@mcw.edu
Phone: (414) 955-8400
Fax: (414) 456-6510
Research Interests
Unprecedented numbers of gene products are now available for study, due to the recent success of large-scale sequencing projects. Characterization of the three-dimensional structures of these proteins is an important part of the ongoing revolution in molecular biology, in new research areas called proteomics, functional genomics and structural genomics. With nuclear magnetic resonance (NMR) spectroscopy as our primary tool, we examine the relationship between biomolecular structure, dynamics and function. NMR is uniquely sensitive to three-dimensional structural arrangements and the fluctuations that proteins and other biomolecules experience as they interact.
A primary focus in the lab is understanding how signaling and adhesion molecules interact with each other to direct the migration and activity of cells involved in immune responses. Many of these molecules are small soluble proteins, like cytokines and chemokines, which are ideal for study by NMR spectroscopy. Others, including selectins, extracellular matrix glycosaminoglycans (GAGs) and membrane-associated receptors are found on the surfaces of cells. All are involved in a vast array of binding reactions that are critical to immune system function. We use NMR and other biophysical and biochemical methods to study the detailed molecular interactions that direct signaling pathways within and between cells.
As a partner in the Center for Eukaryotic Structural Genomics, we are working to develop and apply streamlined methods for the acquisition and analysis of NMR data for the determination of three-dimensional protein structures. With a cryoprobe-equipped 600 MHz NMR spectrometer we can collect complete structural datasets in a small fraction of the time required with conventional instrumentation. When coupled with new software tools designed to automate most of the routine tasks in the data analysis pathway, we hope to contribute to a rapid maturation in the standard methodology for structural protein NMR.
Specific systems under investigation in the lab include:
Selected Publications
"Altered dimer interface decreases stability in an amyloidogenic protein." E.M. Baden, B.A.L. Owen, F.C. Peterson, B.F. Volkman, M. Ramirez-0Alvardo and J.R. Thompson. J. Biol. Chem. (2008) In press
"Interconversion between two unrelated protein folds in the lymphotactin native states." R.L. Tuinstra, F.C. Peterson, E.S. Elgin and B.F. Volkman. Proc. Natl. Acad. Sci. USA (2008) In press
"Solution structure of ZNF593 from Homo sapiens." P.L. Hayes, B.L. Lytle, B.F. Volkman and F.C. Peterson. Protein Sci., 17: 571-576 (2008).
"Solution structure of At3g28950 from Arabidopsis thaliana." N.B. De la Cruz, F.C. Peterson and B.F. Volkman. Proteins, 72: 546-555 (2008).
"Structures of proteins of biomedical interest from the Center for Eukaryotic Sturctural Genomics." G.N. Phillips Jr., B.G. Fox, J.L. Markley, B.F. Volkman, E. Bae, E. Bitto, C.A. Bingman, R.O. Frederick, J.G. McCoy, B.L. Lytle, B.S. Pierce, J. Song and S.N. Twigger. J. Struct. Func. Genomics, 8: 73-84 (2007).
"Solution structure of a membrane-anchored ubiquitin-fold (MUB) protein from Homo sapiense." N.B. De la Cruz, F.C. Peterson, B.L. Lytle, and B.F. Volkman. Protein Sci. 16: 1479-84 (2007).
"An engineered second disulfide bond restricts lymphotactin/XCL1 to a chemokine-like conformation with XCR1 agonist activity." R. Tuinstra, E.S. Elgin, F.C. Peterson and B.F. Volkman. Biochemistry 46 2564-2573 (2007).
"Multiple independent WIP recognition motifs are required for a functional interaction with N-WASP." F.C. Peterson, Q. Deng, M. Zettl, K.E. Prehoda, W.A. Lim, M. Way and B.F. Volkman. J Biol Chem 282 8446-8453 (2007).
"On-column refolding of recombinant chemokines for NMR studies and biological assays." C.T. Veldkamp, F.C. Peterson, P.L. Hayes, J. Mattmiller, J.C. Haugner, N. De la Cruz and B.F. Volkman, Protein Expr Purif 52 202-209 (2007).
"Structural determinants involved in the regulation of CXCL14/BRAK expression by the 26S proteasome." F.C. Peterson, A.G Harder, J.A. Thorpe, B.F. Volkman and S.R. Schwarze. J Mol Biol 363 813-822(2006).
"The first structure of a protein from the SOUL/HBP family: murine p22HBP." J.S. Dias, A.L. Macedo, G.C. Ferreira, F.C. Peterson, B.F. Volkman and B.J. Goodfellow. J Biol Chem 281 10461-73 (2006).
"Solution structure of the MZF1/ZNF42 SCAN domain homodimer." F.C. Peterson, P.L. Hayes, J.K. Waltner, A.K. Heisner, D. R. Jensen, T.L. Sander and B.F. Volkman. J Mol Biol 363 137-47 (2006).
"γ-Glutamylcysteine Synthetase – Glutathione Synthetase: Domain Structure and Identification of Residues Important in Substrate and Glutathione Binding." B.E. Janowiak, M.A. Hayward, F.C. Peterson, B.F. Volkman and O.W. Griffith. Biochemistry 45 10461-73 (2006).
"Solution structure of Arabidopsis thaliana protein At5g39720.1, a member of the AIG2-like protein family." B.L. Lytle, F.C. Peterson, E.M. Tyler, C.L. Newman, D.A. Vinarov, J.L. Markley and B.F. Volkman. Acta Crystallograph Sect F 62 490-3 (2006).
"Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1α (SDF-1αCXCL12)." C.T. Veldkamp, C. Seibert, F.C. Peterson, T.P. Sakmar and B.F. Volkman. J Mol Biol 359 1400-9 (2006).
"Structure of the B3 domain from Arabidopsis thaliana protein At1g16640." J.K Waltner, F.C. Peterson, B.L. Lytle and B.F. Volkman. Protein Sci 14 2478-83 (2005).
"Solution structure of thioredoxin h1 from Arabidopsis thaliana." F.C. Peterson, B.L. Lytle, E. Tyler, D.A. Vinarov, J.L. Markley and B.F. Volkman. Protein Sci, 14 2195-2200 (2005).
"The monomer-dimer equilibrium of Stromal Cell Derived Factor-1 is altered by pH and phosphate, sulfate, and heparin binding." C.T. Veldkamp, F.C. Peterson, A. Pelzek and B.F. Volkman. Protein Sci, 14 1071-81 (2005).
"Cell-free protein production and labeling protocol for NMR-based structural proteomics." D.A. Vinarov, B.L. Lytle, F.C. Peterson, E. Tyler, B.F. Volkman and J.L Markley. Nat Meth 1 149-153 (2004).
"Solution structure of a ubiquitin-like domain from tubulin-binding cofactor B." B.L. Lytle, F.C. Peterson, S.H. Qiu, M. Luo, Q. Zhao, J.L. Markley and B.F. Volkman. J. Biol. Chem. 279: 46787-93. (2004).
"Cdc42 Regulates the Par-6 PDZ Domain Through an Allosteric CRIB-PDZ Transition." F.C. Peterson, R.R. Penkert, B.F. Volkman and K.E. Prehoda. Mol Cell 13 665-676 (2004).
"A glycosaminoglycan recognition element of Lymphotactin essential for in vivo chemokine activity." F.C. Peterson, E.S. Elgin, T.J. Nelson, F. Zhu, T.J. Hoeger, R.J. Linhardt and B.F. Volkman. J Biol Chem 279 12598-12604 (2004).
"A novel zinc-finger is required for Mcm10 homocomplex assembly." C.R. Cook, G. Kung, F.C. Peterson, B.F. Volkman and M. Lei. J. Biol. Chem. 278: 36051-8. (2003).
"Structure of the N-WASP EVH1 Domain-WIP Complex: Insight into the Molecular Basis of Wiskott-Aldrich Syndrome." B.F. Volkman, K.E. Prehoda, J.A. Scott, F.C. Peterson and W.A. Lim. Cell, 111: 565-576. (2002).
"Conformational rearrangement in the C chemokine lymphotactin." E.S. Kuloglu, C.D. Pauza, J.L. Markley and B.F. Volkman. J. Biol. Chem, 277, 17863-17870 (2002).
"Staphylococcal superantigens induce lymphotactin production by human CD4+ and CD8+ T cells." I. Tikhonov, M. Kitabwalla, M. Wallace, M. Malkovsky, B.F. Volkman and C.D. Pauza. Cytokine, 16: 73-78. (2001).
"Monomeric Solution Structure of the Prototypical 'C' Chemokine Lymphotactin." E.S. Kuloglu, D.R. McCaslin, M. Kitabwalla, C.D. Pauza, J.L. Markley and B.F. Volkman. Biochemistry 40: 12486-12496. (2001).
"Solution structure of a type I dockerin domain, a novel prokaryotic, extracellular calcium-binding domain." B.L. Lytle, B.F. Volkman, W.M. Westler, and J.H.D. Wu. J. Mol. Biol. 307: 745-753. (2001).
"Two-state allosteric behavior in a single domain signaling protein." B.F. Volkman, D. Lipson, D.E. Wemmer, and D. Kern. Science 291: 2429-2433. (2001).
"Structure of a transiently phosphorylated switch in bacterial signal transduction." D. Kern, B.F. Volkman, P. Luginbuhl, M.J. Nohaile, S. Kustu and D.E. Wemmer. Nature, 402: 894-898. (1999).