Faculty Profile

Fields of Study

Catalysis of Protein Folding

Areas of Focus

Biochemistry
Cell Biology
Microbiology

Research Interest

Protein folding catalysts and laboratory evolution.

About James Bardwell

Proteins start life as linear amino acid sequences and end up as beautifully folded, active structures. Dr. Bardwell's laboratory focuses on recently discovered machinery that drives protein folding in the cell. Two types of folding helpers are being studied: the catalysts responsible for disulfide bond formation, and the heat shock proteins, which chaperone protein folding. Powerful genetic, structural, and biophysical tools are being used to generate a detailed picture of how these folding machines work.

Dr. Bardwell received his Ph.D. from the University of Wisconsin at Madison in 1987 and was a postdoctoral fellow at Harvard Medical School. He has been a Fellow of the Alexander von Humboldt Foundation and held a Visiting Professor appointment in Regensburg, Germany.

View James Bardwell's C.V.

Publications

Ren G, Stephan D, Xu Z, Zheng Y, Tang D, Harrison RS, Kurz M, Jarrott R, Shouldice SR, Hiniker A, Martin JL, Heras B, Bardwell JC. (2009). "Properties of the thioredoxin fold superfamily are modulated by a single amino acid residue." J Biol Chem. 284(15):10150-9. Read Publication.

Tapley TL, Körner JL, Barge MT, Hupfeld J, Schauerte JA, Gafni A, Jakob U, Bardwell JC. (2009). "Structural plasticity of an acid-activated chaperone allows promiscuous substrate binding." Proc Natl Acad Sci U S A 106(14):5557-62. Read Publication.

Mamathambika BS, Bardwell JC (2008). "Disulfide-linked protein folding pathways." Annu Rev Cell Dev Biol 24:211-35. Review Read Publication.

Pan JL, Sliskovic I, Bardwell JC. (2008). "Mutants in DsbB that appear to redirect oxidation through the disulfide isomerization pathway." J Mol Biol 377(5):1433-42. Read Publication.

Vertommen D, Depuydt M, Pan J, Leverrier P, Knoops L, Szikora JP, Messens J, Bardwell JC, Collet JF. (2008). "The disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD-independent manner." Mol Microbiol 67(2):336-49. Read Publication.

Gleiter S, Bardwell JC. (2008). "Disulfide bond isomerization in prokaryotes." Biochim Biophys Acta 1783(4):530-4. Read Publication.

Masip L, Klein-Marcuschamer D, Quan S, Bardwel JC, Georgiou G (2008). "Laboratory evolution of Escherichia coli thioredoxin for enhanced catalysis of protein oxidation in the periplasm reveals a phylogenetically conserved substrate specificity determinant. ." J Biol Chem 283(2):840-8. Read Publication.

Quan S, Schneider I, Pan J, Von Hacht A, Bardwell JC (2007). "The CXXC motif is more than a redox rheostat." J Biol Chem 282(39):38823-33. Read Publication.

Tapley TL, Eichner T, Gleiter S, Ballou DP, Bardwell JC (2007). "Kinetic characterization of the disulfide bond-forming enzyme DsbB." J Biol Chem 282(14):10263-71. Read Publication.

Hiniker A, Vertommen D, Bardwell JC, Collet JF (2006). "Evidence for Conformational Changes within DsbD: Possible Role for Membrane-Embedded Proline Residues." J. Bacteriol. Oct;188(20):7317-20. Read Publication.

Pan JL, Bardwell JC (2006). "The origami of thioredoxin-like folds." Protein Sci. Oct;15(10):2217-27. Read Publication.

Hiniker A, Collet JF, Bardwell JC (2005). "Copper stress causes an in vivo requirement for the Escherichia coli disulfide isomerase DsbC." J. Biol. Chem. Oct 7;280(40):33785-91. Epub 2005 Aug 8. Read Publication.

Collet JF, Peisach D, Bardwell JC, Xu Z (2005). "The crystal structure of TrxA(CACA): Insights into the formation of a [2Fe-2S] iron-sulfur cluster in an Escherichia coli thioredoxin mutant." Protein Sci. Jul;14(7):1863-9. Read Publication.

Collet, J-F. and Bardwell J.C.A. (2005). "The Catalysis of disulfide bond formation in Prokaryotes." In Protein Folding Handbook, Buchner/Kiefhaber Eds. Wiley-VCH

Tan, J. Lu Y., and Bardwell J.C.A. (2005). "Mutational Anlysis of the disulfide catalysts DsbA and DsbB." J.Bacteriol. 187: 1504-10. Read Publication.

Bardwell J.C.A. (2005). "The dance of disulfide formation." Nat. Struct. Mol. Biol. 11: 582-3. Read Publication.

Bardwell J.C.A. (2005). "Thiol modifications in a snapshot." Nat. Biotechno. 23: 42-3. Read Publication.

Nakamoto H, Bardwell JC. (2004). "Catalysis of disulfide bond formation and isomerization in the Escherichia coli periplasm." Biochim. Biophys. Acta Nov 11;1694(1-3):111-9. Read Publication.

Tan JT, Bardwell JC. (2004). "Key players involved in bacterial disulfide-bond formation." Chembiochem Nov 5;5(11):1479-87. Read Publication.

Hiniker A, Bardwell JC. (2004). "Disulfide relays between and within proteins: the Ero1p structure." Trends Biochem. Sci. Oct;29(10):516-9. Read Publication.

Kadokura H, Tian H, Zander T, Bardwell JC, and Beckwith J (2004). "Snapshots of DsbA in Action: detection of proteins in the process of oxidative folding." Science 303(5657):534-537. Read Publication.

Masip L, Pan JL, Haldar S, Penner-Hahn J, Georgiou G, Bardwell JC, and Collet Jean-Francois (2004). "An Engineered pathway for the formation of protein disulfide bonds." Science 303:1185 - 1189. Read Publication.

Hiniker A and Bardwell JC (2004). "in vivo substrate specificity of periplasmic disulfide oxidoreductases." J. Biol. Chem. Mar 26;279(13):12967-73. Epub 2004 Jan 15. Read Publication.

Goulding CW, Apostol MI, Gleiter S, Parseghian A, Bardwell J, Gennaro M, and Eisenberg D (2004). "Gram-positive DsbE proteins function differently from gram-negative DsbE homologs: A structure function analysis of DsbE from Mycobacterium tuberculosis." J. Biol. Chem. 279: 3516-24. Read Publication.

Hiniker, A. and Bardwell J.C.A. (2004). "Disulfide relays between and within proteins: the Erolp structure." Trends in Biochem. Sci. 29:516-9.

Nakamoto, H. and Bardwell J.C.A. (2004). "Catalysis of Disulfide Bond Formation and Isomerization in the Bacterial Periplasm." Biochim. Biophys. Acta 1694:111-9.

Kadokura H., Tian H., Zander T., Bardwell J.C., and Beckwith J. (2004). "Snapshots of DsbA in Action: detection of proteins in the process of oxidative folding." Science 303(5657):534-537.

Hiniker A. and Bardwell J.C. (2004). "in vivo substrate specificity of periplasmic disulfide oxidoreductases." J. Biol. Chem. 2004 Mar 26;279(13):12967-73. Epub 2004 Jan 15. Read Publication.

Collet J-F. and Bardwell J.C.A. (2003). "Oxidative folding in Bacteria." NATO Science series

Collet J.F., D'Souza J.C., Jakob U., Bardwell J.C. (2003). "Thioredoxin 2, an oxidative stress-induced protein, contains a high affinity zinc binding site." J. Biol. Chem. 278(46):45325-32. Read Publication.

Regeimbal J., Gleiter, S., Trumpower, B.L., Yu, C.A., Diwakar, M., Ballou, D.P., and Bardwell, J.C. (2003). "Disulfide bond formation involves a quinhydrone-type charge-transfer complex." Proc. Nat. Acad. of Sci USA. 100(24):13779-84. Read Publication.

Goulding CW, Apostol MI, Gleiter S, Parseghian A, Bardwell J, Gennaro M, and Eisenberg D (2003). "Gram-positive DsbE proteins function differently from gram-negative DsbE homologs: A structure function analysis of DsbE from Mycobacterium tuberculosis." J. Biol. Chem. 2004 Jan 30;279(5):3516-24. Epub 2003 Nov 3. Read Publication.

Hiniker A. and Bardwell J.C. (2003). "Disulfide bond isomerization in prokaryotes." Biochemistry Feb 11;42(5): 1179-85. Read Publication.

Bardwell J.C. (2002). "Disulfide bond formation, a race between FAD and oxygen." Dev. Cell. Dec;3(6):758-60. Read Publication.

Regeimbal J. and Bardwell J.C. (2002). "DsbB catalyzes disulfide bond formation de novo." J. Biol. Chem. Sep 6;277(36):32706-13. Read Publication.

Collet J.F., Reimer J., Bader M.W., and Bardwell J.C. (2002). "Reconstitution of a disulfide isomerization system." J. Biol. Chem. Jul 26;277(30):26886-92. Read Publication.

Tan J., Jakob U., and Bardwell J.C. (2002). "Overexpression of two different GTPases rescues a null mutation in a heat-induced rRNA." J. Bacteriol. May;184(10):2692-8. Read Publication.

Collet J.F. and Bardwell J.C. (2002). "Oxidative protein folding in bacteria." Mol. Microbiol. Apr;44(1):1-8. Read Publication.

Xie T, Yu L, Bader MW, Bardwell JC, and Yu CA (2002). "Identification of the ubiquinone-binding domain in the disulfide catalyst disulfide bond protein B." J. Biol. Chem. Jan 18;277(3):1649-52. Read Publication.

Collet J.F. and Bardwell J.C. (2002). "Disulfides out of thin air." Nat. Struct. Biol. Jan;9(1):2-3. Read Publication.

Bader, MW and Bardwell JC (2001). "Catalysis of disulfide bond formation and isomerization in Escherichia coli." Adv. Protein Chem. 59:283-301. Read Publication.

Goldstone D., Haebel P.W., Katzen F., Bader M.W., Bardwell J.C., Beckwith J., and Metcalf P. (2001). "DsbC activation by the N-terminal domain of DsbD." Proc. Natl. Acad. Sci. USA. Aug 14;98(17):9551-6. Read Publication.

Graumann J, Lilie H, Tang X, Tucker KA, Hoffman JH, Vijayalakshmi J, Saper M, Bardwell JC, and Jakob U (2001). "Activation of the redox-regulated molecular chaperone Hsp33-a two-step mechanism." Structure (Camb) May 9;9(5):377-87. Read Publication.

Bader M.W., Hiniker A., Regeimbal J., Goldstone D., Haebel P.W., Riemer J., Metcalf P., and Bardwell J.C. (2001). "Turning a disulfide into an oxidase: DsbC mutants that imitate DsbA." EMBO J. Apr 2;20(7):1555-62. Read Publication.

Bessette PH, Qiu J, Bardwell JC, Swartz JR, and Georgiou G (2001). "Effects of sequences of the active-site dipeptides of DsbA and DsbC on in vivo folding of multidisulfide protein in Escherichia coli." J. Bacteriol. Feb;183(3):980-8. Read Publication.

Jakob U, Eser M, and Bardwell JC (2000). "Redox switch of hsp33 has a novel zinc-binding motif." J. Biol. Chem. Dec 8;275(34):38302-10. Read Publication.

Kadokura H., Bader M., Tian H., Bardwell J.C., and Beckwith J (2000). "Roles of a conserved arginine residue of DsbB in linking protein disulfide-bond-formation pathway to the respiratory chain in Escherichia coli." Proc. Natl. Acad. Sci. USA. Sep 26;97(20):10884-9. Read Publication.

Bader M.W., Xie T., Yu C.A., and Bardwell J.C. (2000). "Disulfide bonds are generated by quinone reduction." J Biol Chem. Aug 25;275(34):26082-8. Read Publication.

Bugl H, Fauman EB, Staker BL, Zheng F, Kushner SR, Saper MA, Bardwell JC, and Jakob U (2000). "RNA methylation under heat shock control." Mol. Cell. Aug;6(2):349-60. Read Publication.

Shao F., Bader M.W., Jakob U., and Bardwell J.C. (2000). "DsbG, a protein disulfide isomerase with chaperone activtity." J. Biol. Chem. May 5;275(18):13349-52. Read Publication.

Wong C, Sridhara S, Bardwell JC, and Jakob U (2000). "Heating greatly speeds Coomassie blue staining and destaining." Biotechniques Mar;28(3):426-28,430,432. Read Publication.

Korber P., Stahl J.M., Nierhaus K.H., and Bardwell J.C. (2000). "Hsp15: a ribosome-associated heat shock protein." EMBO J. Feb 15;19(4):741-8. Read Publication.

Staker BL, Korber P, Bardwell JC, and Saper MA. (2000). "Structure of Hsp15 reveals a novel RNA-binding motif." EMBO J. Feb 15;19(4):749-57. Read Publication.

Bader M, Winther JR, and Bardwell JC (1999). "Protein oxidation: prime suspect found 'not guilty'." Nat Cell Biol. Jul;1(3):E57-8. Read Publication.

Bader M., Muse W., Ballou D.P., Gassner C., and Bardwell J.C. (1999). "Oxidative protein folding is driven by the electron transport chain." Cell Jul 23;98(2):217-27. Read Publication.

Jakob U., Muse W., Eser M., and Bardwell J.C. (1999). "Chaperone activity with a redox switch." Cell Feb 5;96(3):341-52. Read Publication.

Korber P., Zander T., Herschlag D., and Bardwell J.C. (1999). "A new heat shock protein that binds nucleic acids." J Biol Chem. Jan 1;274(1):249-56. Read Publication.

Guddat LW, Bardwell JC, and Martin JL. (1998). "Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stability." Structure Jun 15;6(6):757-767. Read Publication.

Bader M, Muse W, Zander T, and Bardwell J. (1998). "Reconstitution of a protein disulfide catalytic system." J Biol Chem Apr 24;273(17):10302-7. Read Publication.

Zander T, Phadke ND, and Bardwell JC (1998). "Disulfide bond catalysts in Escherichia coli." Methods Enzymol. 290:59-74. Read Publication.

Guddat LW, Bardwell JC, Glockshuber R, Huber-Wunderlich M, Zander T, and Martin JL (1997). "Structural analysis of three His32 mutants of DsbA: support for an electrostatic role in His32 in DsbA stability." Protein Sci Sep;6(9):1893-900. Read Publication.

Guddat LW, Bardwell JC, Zander T, and Martin JL. (1997). "The uncharged surface features surrounding the active site of Escherichia coli DsbA are conserved and are implicated in peptide binding." Protein Sci. Jun;6(6):1148-56. Read Publication.

Grauschopf U, Winther JR, Korber P, Zander T, Dallinger P, and Bardwell JC (1995). "Why is DsbA such an oxidizing disulfide catalyst?" Cell. Dec 15;83(6):947-55. Read Publication.

Jakob U, Meyer I, Bugl H, Andre S, Bardwell JC, and Buchner J. (1995). "Structural organization of procaryotic and eucaryotic Hsp90. Influence of divalent cations on structure and function." J Biol Chem Jun 16;270(24):14412-9. Read Publication.

Bardwell JC. (1994). "Building bridges:disulphide bond formation in the cell." Mol Microbiol. Oct;14(2):199-205. Read Publication.

Martin JL, Bardwell, and Kuriyan J. (1993). "Crystal structure of the DsbA protein required for disulphide bond formation in vivo." Nature Sep 30;365(6445):464-8. Read Publication.

Bardwell JC and Beckwith J. (1993). "The bonds that tie: catalyzed disulfide bond formation." Cell Sep 10;74(5):769-71. Read Publication.

Zapun A, Bardwell JC, and Creighton TE (1993). "The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo." Biochemistry May 18;32(19):5082-92. Read Publication.

Martin JL, Waksman G, Bardwell JC, Beckwith J, and Kuriyan J. (1993). "Crystallization of DsbA, an Escherichia coli protein required for disulphide bond formation in vivo." J Mol Biol. Apr 5;230(3):1097-100. Read Publication.

Bardwell JC, Lee JO, Jander G, Martin N, Belin D, and Beckwith J. (1993). "A pathway for disulfide bond formation in vivo." Proc Natl Acad Sci USA Feb 1;90(3):1038-42. Read Publication.

Bardwell JC, McGovern K, and Beckwith J. (1991). "Identification of a protein required for disulfide bond formation in vivo." Cell Nov 1;67(3):581-9. Read Publication.

Yeung T, Mullin DA, Chen KS, Craig EA, Bardwell JC, and Walker JR (1990). "Sequence and expression of the Escherichia coli recR locus." J Bacteriol. Oct;172(10):6042-7. Read Publication.

Chen SM, Takiff HE, Barber AM, Dubois GC, Bardwell JC, and Court DL. (1990). "Expression and characterization of RNase III and Era proteins. Products of the rnc operon of Escherichia coli." J Biol Chem Feb 15;265(5):2888-95. Read Publication.

Bardwell JC, Regnier P, Chem SM, Nakamura Y, Grunberg-Manago M, Court DL. (1989). "Autoregulation of RNase III operon by mRNA processing." EMBO J. Nov;8(11):3401-7. Read Publication.

Bardwell JC and Craig EA (1988). "Ancient heat shock gene is dispensable." J Bacteriol Jul;170(7):2977-83. Read Publication.

Bardwell JC and Craig EA. (1987). "Eukaryotic Mr 83,000 heat shock protein has a homologue in Escherichia coli." Proc Natl Acad Sci USA Aug;84(15):5177-81. Read Publication.

Bardwell JC, Tilly K, Craig E, King J, Zylicz M, and Georgopoulos C. (1986). "The nucleotide sequence of the Escherichia coli K12 dnaJ+ gene.  A gene that encodes a heat shock protein." J Biol Chem. Feb 5;261(4):1782-5. Read Publication.

Cowing DW, Bardwell JC, Craig EA, Woolford C, Hendrix RW, and Gross CA (1985). "Consensus sequence for Escherichia coli heat shock gene promoters." Proc Natl Acad Sci USA May;82(9):2679-83. Read Publication.

Bardwell JC and Craig EA. (1984). "Major heat shock gene of Drosophila and the Escherichia coli heat-inducible dnaK gene are homologous." Proc Natl Acad Sci USA Feb;81(3):848-52. Read Publication.