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Education and Training:

B.Eng., Polymer Materials and Sciences, Chengdu University of Science and Technology, China
Ph.D., Chemistry/Polymer Physics, Louisiana State University (with Paul Russo)
Postdoctoral, Molecular Biophysics and Biochemistry, Yale University (with Donald Engelman)

Research:

We study the structure and dynamics of cell signaling proteins. We are particularly interested in signaling proteins that control cell-cell adhesion, and the assembly and intracellular trafficking of membrane receptors and ion channels. These proteins function as molecular machines and switches, which can fail to work properly for various reasons, causing diseases such as cancer and cystic fibrosis. We employ a variety of biochemical and cell biological experiments, as well as biophysical and structural biology techniques, including small angle X-ray and neutron scattering, to study the interactions of these proteins

We also utilize quasielastic neutron scattering, particularly neutron spin echo spectroscopy, to study protein dynamics and protein domain motion. We have developed a theoretical framework using statistical mechanics to interpret the NSE data. These methods allow us to see, for the first time, the structure and dynamics of significant protein interactions on nanoscales. NSE fills an important information gap in our ability to study protein motion on sub-microsecond time scales and on nanomenter length scales.

Lab Members:
Jeong Ho Ju, Ph.D., Staff scientist
Jahan Ali Khajeh, Ph.D., Postdoctoral associate
Natalia Orlova, Ph.D. graduate student
Budo Zdravkovic, Ph.D. graduate student
Moussoubaou Atchiba, master student

Undergraduate students:
Karina Li-Fang
Haoyu Sun
Mingxi Yang

Publications

Bhattacharya, S, Ju, JH, Orlova, N, Khajeh, JA, Cowburn, D, Bu, Z., Ligand induced dynamics changes in extended PDZ domains from NHERF1, J Mol Biol, in press

Callaway, DJ, Farago, B, Bu, Z., Nanoscale protein dynamics: A new frontier for neutron spin echo spectroscopy, The European Physical Journal E-Soft Matter & Biological Physics, in press

Jayasundar JJ, Ju JH, He L, Liu D, Meilleur F, Zhao J, Callaway DJ, Bu Z., Open Conformation of Ezrin Bound to Phosphatidylinositol 4,5-Bisphosphate and to F-actin Revealed by Neutron Scattering., J. Bio. Chem. 287:37119-33, 2012

Bu, Z. and Callaway, D.J.E., Proteins MOVE! Protein dynamics and long-range allostery in cell signaling, Adv Protein Chem Struct Biol. 83:163-221, 2011

Farago, B., Li, J., Cornilescu, G., Callaway, D.J.E., Bu, Z. Activation of nanoscale allosteric protein domain motion revealed by neutron spin echo spectroscopy. Biophys J. 99:3473-82, 2010

Bhattacharya, S., Dai, Z., Li, J., Baxter, S., Callaway, D.J., Cowburn, D., Bu, Z. A conformational switch in the scaffolding protein NHERF1 controls autoinhibition and complex formation. J. Bio. Chem. 285:9981-94, 2010

Li, J., Callaway, D.J., Bu, Z. Ezrin induces long-range interdomain allostery in the scaffolding protein NHERF1. J. Mol. Biol. 392(1):166-80, 2009

Cheng H, Li J, Fazlieva R, Dai Z, Bu Z, Roder H. Autoinhibitory interactions between the PDZ2 and C-terminal domains in the scaffolding protein NHERF1. Structure 17(5):660-9, 2009

Li, J., Poulikakos, P.I., Dai, D., Testa, J.R., Callaway,D.J., Bu, Z. PKC phosphorylation disrupts NHERF autoinhibition and promotes CFTR macromolecular assembly. J. Bio. Chem. 282:27086-27099, 2007

Dawson, J.B., Bu, Z. (co-corresponding), Lemmon, M.A. Ligand-induced structural transitions in ErbB receptor extracellular domains. Structure 15:942-954, 2007.

Bu, Z., Shi, Y., Callaway, D.J., Tycko, R. Molecular alignment within b sheets in Ab14-23 fibrils: solid state NMR experiments and theoretical predictions. Biophys. J. 92:594-602, 2007.

Samuel, D., Cheng, H., Riley, P.W., Canutescu, A.A., Nagaswami, C., Weisel, J.W., Bu, Z., Walsh, P.N., Roder, H. Solution structure of the A4 domain of factor XI sheds light on the mechanism of zymogen activation. Proc. Natl. Acad. Sci. U.S.A. 104:15693, 2007.

Fang, M., Cheng, H., Dai, Z., Bu, Z., Sigal, L.J. Immunization with a single extracellular enveloped virus protein produced in bacteria provides partial protection from a lethal Orthopoxvirus infection in a natural host. Virology 345:231-43, 2006.

Shi, Y., Stouten, P.F.W., Pillalamarri, N., Barile, L., Rosal, R.V., Teichberg, S., Bu, Z. (co-corresponding), Callaway, D.J. Quantitative determination of the topological propensities of amyloidogenic peptides. Biophys. Chem. 120:55-61, 2006.

Bu, Z. (co-corresponding), Biehl, R., Monkenbusch, M., Richter, D., Callaway, D.J. Coupled protein domain motion in Taq DNA polymerase revealed by neutron spin echo spectroscopy. Proc. Natl. Acad. Sci. U.S.A. 102:17646-17651, 2005.

Li, J., Dai, Z., Jana, D., Callaway, D.J.E., Bu, Z. Ezrin controls the macromolecular complexes formed between an adaper protein Na+/H+ exchanger regulatory factor and the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 280:37634-37643, 2005.

Ho, D.L., Byrnes, W.M., Ma, W.P., Shi, Y., Callaway, D.J.E., Bu, Z. Structure-specific DNA-induced conformational changes in Taq polymerase revealed by small angle neutron scattering. J. Biol. Chem. 279:39146-39154, 2004.

Laksanalamai, P., Jiemjit, A., Bu, Z., Maeder, D.L., Robb, F.T. Multi-subunit assembly of the Pyrococcus furiosus small heat shock protein is essential for cellular protection at high temperature. Extremophiles 7:79-83, 2003.

Bu, Z., Wang, L., Kendall, D.A. Nucleotide binding induces changes in the oligomeric state and conformation of Sec A in a lipid environment: a small-angle neutron-scattering study. J. Mol. Biol. 332:23-30, 2003.

Tjernberg, L.O., Tjernberg, A., Bark, N., Shi, Y., Ruzsicska, B.P., Bu, Z., Thyberg, J., Callaway, D.J.E. Assembling amyloid fibrils from designed structures containing a significant amyloid b-peptide fragment. Biochem. J. 366:343-351, 2002. PMCID: PMC1222771

Bu, Z. (corresponding), Cook, J., Callaway, D.J.E. Dynamic regimes and correlated structural dynamics in native and denatured alpha-lactalbumin. J. Mol. Biol. 312:865-873, 2001.

Hanakahi, L.A., Bu, Z., Maizels, N. The C-terminal domain of nucleolin accelerates nucleic acid annealing. Biochemistry 39:15493-15499, 2000.

Bu, Z. (corresponding), Neumann, D.A., Lee, S.-H., Brown, C.M., Engelman, D.M., Han, C.C. A view of dynamics changes in the molten globule-native folding step by quasielastic neutron scattering. J. Mol. Biol. 301:525-536, 2000.

Koide, S., Huang, X., Link, K., Koide, A., Bu, Z., Engelman, D.M. Design of single-layer b-sheets without a hydrophobic core. Nature 403:456-460, 2000.

Bu, Z., Engelman, D.M. A method for determining transmembrane helix association and orientation in detergent micelles using small angle x-ray scattering. Biophys. J. 77:1064-1073, 1999. PMCID: PMC1300396

Koide, S., Bu, Z., Risal, D., Pham, T.-N., Nakagawa, T., Tamura, A., Engelman, D.M. Multistep denaturation of Borrelia burgdorferi OspA, a protein containing a single-layer b-sheet. Biochemistry 38:4757-4767, 1999.

Russo, P.S., Baylis, M., Bu, Z., Stryjewski, W., Doucet, G., Temyanko, E., Tipton, D. Self-diffusion of a semiflexible polymer measured across the lyotropic liquid-crystalline-phase boundary. J. Chem. Phys. 111:1746-1752, 1999.

Bu, Z., Koide, S., Engelman, D.M. A solution SAXS study of Borrelia burgdorferi OspA, a protein containing a single-layer b-sheet. Protein Sci. 7:2681-2683, 1998. PMCID: PMC2143892

Bu, Z., Perlo, A., Johnson, G.E., Olack, G., Engelman, D.M., Wyckoff, H.W. A small angle x-ray scattering apparatus for studying biological macromolecules in solution. J. Appl. Cryst. 31:533-543, 1998.

Lemmon, M.A., Bu, Z., Ladbury, J.E., Zhou, M., Pinchasi, D., Lax, I., Engelman, D.M., Schlessinger, J. Two EGF molecules contribute additively to stabilization of the EGFR dimer. EMBO J. 16:281-294, 1997. PMCID: PMC1169635

Cush, R., Russo, P.S., Kucukyavuz, Z., Bu, Z., Neau, D., Shih, D., Kucukyavuz, S., Ricks, H. Translational and rotational diffusion of rodlike virus in random coil solutions. Macromolecules 30:4920-4926, 1997.

Smith, C.K., Bu, Z., Anderson, K.S., Sturtevant, J.M., Engelman, D.M., Regan, L. Surface point mutations that significantly alter the structure and stability of a protein's denatured state. Protein Sci. 5:2009-2019, 1996. PMCID: PMC2143264

Rodgers, K.K., Bu, Z., Fleming, K.G., Schatz, D.G., Engelman, D.M., Coleman, J.E. A zinc-binding domain involved in the dimerization of RAG1. J. Mol. Biol. 260:70-84, 1996.

Gusev, V.Y., Feng, X., Bu, Z., Haller, G.L., O'Brien, J.A. Mechanical stability of pure silica mesoporous MCM-41 by nitrogen adsorption and small-angle x-ray diffraction measurements. J. Phys. Chem. 100:1985-1988, 1996.

Bu, Z., Russo, P.S., Tipton, D.L., Negulescu, I.I. Self-diffusion of rodlike polymers in isotropic solutions. Macromolecules 27:6871-6881, 1994.

Bu, Z., Russo, P.S. Probe diffusion of dextran in semiflexible hydroxypropylcellulose solutions. Macromolecules 27:1187-1193, 1994.

Wattenbarger, M., Bloomfield, V.A., Bu, Z., Russo, P.S. Tracer diffusion of BSA in DNA solutions. Macromolecules 25:5263-5265, 1992.