Stewart Memorial Professor of Biochemistry and Cell Biology
Examination of protein-DNA interactions involved in regulating gene expression is the major focus of research efforts in this laboratory. Genetic regulation is an essential function in all organisms and provides the ability to respond to signals that reflect environmental conditions, determine developmental processes, and communicate other information within an organism. The lactose repressor (LacI) controls expression of the enzymes that metabolize lactose in E. coli. Our long-term goal is detailed insight into mechanisms by which both LacI recognition and regulation occur, and experiments with collaborators extend the applications of this protein. The Ultrabithorax gene encodes a member of the homeodomain family of proteins (Hox proteins) that participate in specifying segmental identity in the Drosophila embryo during development. Experiments are underway with collaborators to explore regulation of DNA recognition and transcriptional regulation and to understand the interesting materials properties of this protein.
Huang, Z., Lu, Y., Majitha, R., Shah, J., Meissner, K., Matthews, K.S., Bondos, S.E., and Lou, J., Size dictates mechanical properties for protein fibers self-assembled by the Drosophila Hox transcription factor Ubx, Biomacromolecules 11, 3644-3651 (2010).
Jamison, J.A., Bryant, E.L., Kadali, S.B., Wong, M.S., Colvin, V.L., Matthews, K.S., and Calabretta, M.K., Altering protein surface charge with chemical modification modulates protein-gold nanoparticle aggregation, J. Nanopart. Res., in press (DOI 10.1007/s11051-010-0057-S) (2010).
Xu, J., Liu, S., Chen, M., Ma, J., and Matthews, K.S. Altering residues N125 and D149 impacts sugar effector binding and allosteric parameters in Escherichia coli lactose repressor. Biochemistry
Bondos, S.E., Catanese, D.J., Jr., Jordy, K.E., and Matthews, K.S.
Bondos, S.E., Catanese, D.J., Jr., Jordy, K.E., and Matthews, K.S., Network analysis of Drosophila protein interactions: Sorting by protein fold identifies false positives. in preparation
Norton, M., Xu, H., Liu, S., Zhan, H., and Matthews, K.S. Conversion of PurR from dimer to tetramer using the LacI C-terminus: Introduction of DNA looping capacity
. in preparation
Catanese, D.J., Jr., and Matthews, K.S., High affinity, dsRNA binding by disconnected interacting protein 1, Biochem. Biophys. Res. commun. 399, 186-191 (2010).
Falcon, C.M., Swint-Kruse, L., and Matthews K.S., Lactose repressor proteins with increased operator DNA binding affinity, Application 10/197,053, issued as Patent No. 7390645, June 24, 2008.
Zhan, H., Camargo, M., and Matthews, K.S., Positions 94-98 of the lactose repressor N-subdomain monomer•monomer interface are critical for allosteric communication, Biochemistry 49, 8636-8645 (2010).
Fleming, R., Liu, S., Xu, J., Zhan, H., and Matthews, K.S. The hinge helix of lactose repressor protein promotes specific DNA binding. in preparation
Swint-Kruse, L., and Matthews, K.S., lac operon, Encyclopedia of Biological Chemistry, Vol. 2 (Eds., Lennarz, W.J., and Lane, M.D.), 2nd Edition, in press.
Jamison, J.A., Bryant, E.L., Kadali, S.B., Wong, M.S., Colvin, V.L., Matthews, K.S., and Calabretta, M.K. Altering protein surface charge with chemical modification modulates protein-gold nanoparticle aggregation. J. Nanopart. Res., 13 2011: 625-636
Catanese, D.J., and Matthews, K.S. Disconnected Interacting Protein 1 binds with high affinity to pre-tRNA and ADAT. Biochem. Biophys. Res. Commun., 414 2011: 506-511
Huang, Z., Salim, T., Brawley, A., Patterson, J., Matthews, K.S., and Bondos, S.E. Functionalization and patterning of protein-based materials using active Ultrabithorax chimeras. Advanced Functional Materials, 21 2011: 2633-2640
Liu, Y., Merchant, Z., Hsiao, H.-C., Gonzalez, K.L., Matthews, K.S., and Bondos, S.E. Media composition influences yeast one- and two-hybrid results. Biological Procedures Online, 13 2011: 6
Xu, J., Liu, K.-W., Matthews, K.S., and Biswal, S.L. Monitoring DNA binding to Escherichia coli lactose repressor using quartz crystal microbalance with dissipation. Langmuir, 27 2011: 4900-4905
Swint-Kruse, L., and Matthews, K.S. Allostery in the LacI/GalR family: Variations on a theme. Current Opinion in Microbiology, 12 2009: 129-137
Xu, J., and Matthews, K.S. Flexibility in the inducer binding region is crucial for allostery in Escherichia coli lactose repressor. Biochemistry, 48 2009: 4988-4998
Zhan, H., Sun, Z., and Matthews, K.S. Functional impact of polar and acidic substitutions in the lactose repressor hydrophobic monomer•monomer interface with a buried lysine. Biochemistry, 48 2009: 1305-1314
Liu, Y., Matthews, K.S., and Bondos, S.E. Internal regulatory interactions determine DNA binding specificity by a Hox transcription factor. J Mol Biol, 390 2009: 760-774
Ruthauskas, D., Zhan, H., Matthews, K.S., Pavone, F.S., and Vanzi, F. Tetramer opening in LacI-mediated DNA looping. Proc Natl Acad Sci USA, 106 2009: 16627-16632
Greer, A., Huang, Z., Oriakhi, A., Matthews, K., and Bondos, S. The Drosophila transcription factor Ultrabithorax self-assembles into protein-based biomaterials with multiple morphologies. Biomacromolecules, 10 2009: 829-837
Taraban, M., Zahn, H., Whitten, A..E., Langley, D.B., Matthews, K.S., Swint-Kruse, L., and Trewhella, J. Ligand-induced conformational changes and conformational dynamics in the solution structure of the lactose repressor protein. J. Mol. Biol., 376 2008: 466-481
Liu, Y., Matthews, K.S., and Bondos, S.E. Multiple intrinsically disordered sequences after DNA binding by the homeodomain of the Drosophila Hox protein Ultrabithorax. J. Biol. Chem., 283 2008: 20874-20887
Wilson, C.J., Zhan, H., Swint-Kruse, L., and Matthews, K.S. Ligand interactions with lactose repressor protein and the repressor-operator complex: The effects of ionization and oligomerization on binding. Biophys. Chem, 126 2007: 94-105
Wilson, C.J., Zhan, H., Swint-Kruse, L., and Matthews, K.S. The lactose repressor system: Paradigms for transcription regulation, allosteric behavior, and protein folding. Cell. Mol. Life Sci., 64 2007: 3-16
Calabretta, M.K., Matthews, K.S., and Colvin, V.L. DNA binding to protein-gold nanocrystal conjugates. Bioconjugate Chemistry, 17 2006: 1156-1161
Zhan, H., Swint-Kruse, L., and Matthews, K.S. Extrinsic interactions dominate helical propensity in coupled binding and folding of lactase repressor hinge helix. Biochemistry, 45 2006: 5896-5906
Bondos, S.E., Tan, X.X., and Matthews, K.S. Physical and genetic interactions link Hox function with diverse transcription factors and cell signaling proteins. Mol. Cell. Proteomics, 5 2006: 824-834
Calabretta, M., Jamison, J.A., Falkner, J. C., Liu, Y., Yuhas, B.D., Matthews, K.S., and Colvin, V.L. Analytical ultracentrifugation for characterizing nanocrystals and their bioconjugates. Nanoletters, 5 2005: 963-967
Das, P., Wilson, C.J., Fossati, G., Wittung-Stafshede, P., Matthews, K.S., and Clementi, C. Characterization of the folding landscape of monomeric lactose repressor: Quantitative comparison of theory and experiment. Proc. Natl. Acad. Sci. U.S.A., 102 2005: 14569-14574
Zhan, H., Swint-Kruse, L., and Matthews, K.S. Dynamic asymmetry in a protein homodimer: experimental support for a computational prediction. Biochemistry, 44 2005: 11201-11213
Bondos, S.E., Catanese, D.J., Jr., Jordy, K.E., and Matthews, K.S. Network analysis of Drosophila protein interactions: Sorting by protein fold identifies false positives. Biochemistry 2005Submitted
Wilson, C.J., Das, P., Clementi, C., Matthews, K.S., and Wittung-Stafshede, P. The experimental folding landscape of monomeric lactose repressor, a large two-domain protein, involves two kinetic intermediates. Proc. Natl. Acad. Sci. U.S.A., 102 2005: 14563-14568
Swint-Kruse, L., and Matthews, K.S. Gene expression in bacteria: The lac operon. Encyclopedia of Biological Chemistry (Eds., W.J. Lennarz and M. D. Lane), Vol. 2 2004: 529-535
Bondos, S., Tan, X.X., Catanese, D.J., Jr., Ware, A.A., Li, L., and Matthews, K.S. Hox protein Ultrabithorax Ib interacts with disconnected interacting protein, a double-stranded RNA binding protein. J. Biol. Chem., 279 2004: 26433-26444
Swint-Kruse, L., and Matthews, K.S. Thermodynamics, protein modification, and molecular dynamics in characterizing the lactose repressor protein: Strategies for complex analyses of protein structure-function. Methods in Enzymology, Energetics of Biological Macromolecules, Part D (Eds., Holt, J. M., Johnson, M. L., and Ackers, G.K.), 379 2004: 1888-2009
Flynn, T.C., Swint-Kruse, L., Kong, Y., Booth, C., Matthews, K.S., and Ma, J., Allosteric transition pathways in the lactose repressor protein core domains: Asymmetric motions in a homodimer. Protein Science, 12 2003: 2523-2541
Swint-Kruse, L., Zhan, H., Fairbanks, B.M., Maheshwari, A., and Matthews, K.S., Perturbation from a distance: Mutations that alter LacI function through long-range effects. Biochemistry, 42 2003: 14004-14016
Swint-Kruse, L., Larson, C., Pettitt, B.M., and Matthews, K.S. Fine-tuning function: Correlation of hinge domain interactions with functional distinctions between LacI and PurR. Protein Science, 11 2002: 778-794
Nichols, N.M., and Matthews, K.S. Human p53 phosphorylation mimic, S392E, increases nonspecific DNA affinity and thermal stability. Biochemistry, 41 2002: 170-178
Tan, X.X., Li, L., Bondos, S., and Matthews, K.S. Transcription activation by Ultrabithorax Ib protein requires a predicted alpha-helical region. Biochemistry, 41 2002: 2774-2785
Moraitis, M., Xu, H., and Matthews, K.S. Ion Concentration and Temperature Dependence of DNA Binding: Comparison of PurR and LacI Repressor Proteins. Biochemistry, 40 2001: 8109-8117
Swint-Kruse, L., Elam, C.R., Lin, J., Beasley, D., Wycuff, D.R., and Matthews, K.S. Plasticity of Quaternary Structure: Twenty-two Ways To Form a LacI Dimer. Protein Science, 10 2001: 262-276
Nichols, N.M., and Matthews, K.S. Protein-DNA Binding Correlates with Structural Thermostability for the Full-length Human p53 Protein. Biochemistry, 40 2001: 3847-3858
Nichols, N.M., and Matthews, K.S. p53 Unfolding Detected by CD But Not by Tryptophan Fluorescence. Biochemical and Biophysical Research Communications, 288 2001: 111-1115
Wycuff, D.R., and Matthews, K.S. Generation of an AraC-araBAD-regulated T7 Expression System. Analytical Biochemistry, 277 2000: 67-73
Falcon, C.M., and Matthews, K.S. Operator DNA Sequence Variation Enhances High Affinity Binding by Hinge Helix Mutants of Lactose Repressor Protein. Biochemistry, 39 2000: 11074-11083
Matthews, K.S., Falcon, C.M., and Swint-Kruse, L. Relieving Repression. Nature Structural Biology, 7 2000: 184-187
Falcon, C.M., and Matthews, K.S. Glycine Insertion in the Hinge Region of Lactose Repressor Protein Alters DNA Binding. J. Biol. Chem., 274 1999: 30849-30857
Ozarowski, A., Barry, J.K., Matthews, K.S., and Maki, A.H. Ligand-induced Conformation Changes in Lactose Repressor: A Phosphorescence and ODMR Study of Single-tryptophan Mutants. Biochemistry, 38 1999: 6715-6722
Bondos, S., Swint-Kruse, L., and Matthews, K. Protein Folding. McGraw-Hill Yearbook of Science and Technology (M. Licker, Publisher) 1999: 361-363
Barry, J.K., and Matthews, K.S. Substitutions at Histidine 74 and Aspartate 278 Alter Ligand Binding and Allostery in Lactose Repressor Protein. Biochemistry, 38 1999: 3579-3590
Barry, J.K., and Matthews, K.S. Thermodynamic Analysis of Folding and Assembly in Lactose Repressor Protein. Biochemistry, 38 1999: 6520-6528