Linda Nicholson
Professor of Biochemistry and Physical Biochemistry

Phone

607-255-7208

Address

Department of Molecular Biology & Genetics
239 Biotechnology Building
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Background

Linda Nicholson is an Associate Professor of Molecular Biology and Genetics. She received B.Sc. and M. Sc. degrees in Mechanical Engineering from the University of Virginia in 1982 and 1985, respectively. In 1990, she received a Ph.D. in Molecular Biophysics from Florida State University, where she specialized in solid-state NMR studies to uniformly oriented biomolecular systems. As a postdoc at NIH, she worked in the rapidly developing field of multidimensional solution NMR spectroscopy of proteins. She joined the Cornell faculty in 1994.

Research Description

Professor Nicholson's research is funded by a grant from the National Science Foundation, "Establishing the Thermodynamic and Kinetic Thresholds of Bacterial Protein Secretion via the Type 3 Secretion System", and by an NIH R01 grant, "Conformational Dynamics in Pin1 Regulation of APP Processing and Abeta Production".

Life takes place through the concerted flow of numerous biological processes. At the molecular level, this involves highly specific and transient protein-protein and protein-ligand interactions. The specificity and function of a given protein is determined by its unique three-dimensional structure and by motions of groups of atoms within this scaffold. We are interested in observing changes in atomic level structure and dynamics induced by perturbations, such as ligand binding or phosphorylation, that are associated with these transient interactions. Such information provides insights into unanswered questions regarding the origins of binding energy and the mechanisms by which protein function is regulated. These questions are critical in practical endeavors such as drug design and protein engineering.

Our research involves the application of multidimensional NMR spectroscopy to investigate the structure and kinetics of proteins. We are focusing on key proteins that have been shown to play important roles in disease processes such as Alzheimer's disease and pathogen infection.

Publications

Dawson, J. E. and Nicholson, L. K. (2008) Folding kinetics and thermodynamics of Pseudomonas syringae effector protein AvrPto provide insight into translocation via the Type III secretion system, Protein Science, 17,1109 - 1119.

Nicholson, L. K. and Lu, K. P. (2007) Prolyl cis/trans Isomerization as a Molecular Timer in Crk Signaling. Molecular Cell, 25, 483-485.

Lu, K. P., Finn, G., Lee, T. H. and Nicholson, L. K. (2007) Prolyl cis-trans isomerization as a molecular timer, Nature Chem. Biol., 3, 619-629.

Xiao, F., He, P., Abramovich, R. B., Dawson, J. E., Nicholson, L. K., Sheen, J. and Martin, G. B. (2007) The N-terminal region of pseudomonas type III effector AvrPtoB elicits Pto-dependent immunity and has two distinct virulence determinants, Plant J., 52, 595-614.

Jayaraman, B. and Nicholson, L. K. (2007) Thermodynamic Dissection of the Ezrin NFERM/CERMAD Interface, Biochemistry, 46, 12174-12189.

Pastorino, L., Sun, A., Lu, P.-J., Zhou, X. Z., Balastik, M., Finn, G., Wulf, G., Lim, J., Li, S.-H., Li, X., Xia, W., Nicholson, L. K. and Lu, K. P. (2006) The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-b production. Nature 440, 528-534.

Jayaraman, B. and Nicholson, L. K. (2006) Letter to the Editor: Backbone Resonance Assignments of Ezrin C ERMAD in a Non-covalent Complex with Ezrin N FERM, J. Biomol. NMR, 36, 63.

Wulf, J., Pascuzzi, P. E., Fahmy, A., Martin, G. E. and Nicholson, L. K. (2004) The solution structure of type III effector protein AvrPto reveals conformational and dynamic features important for plant pathogenesis. Structure 12, 1257 1268.

Wulf, J., Pascuzzi, P., Martin, G. B. and Nicholson, L. K. (2002) 1H, 15N and 13C chemical shift assignments of the structured core of the pseudomonas effector protein AvrPto. J. Biomol. NMR 23, 247-248.

Pawley, N. H., Koide, S., and Nicholson, L. K. (2002) Backbone Dynamics and Thermodynamics of Borrelia Outer Surface Protein A. J. Mol. Biol. 324, 991-1002.

Pawley, N. H., Gans, J. D. and Nicholson, L. K. (2002) Factors determining the reliable description of global tumbling parameters in solution NMR. J. Biomol. NMR 24, 215-229.

Ramelot, T. A. and Nicholson, L. K. (2001) Phosphorylation-Induced Structural Changes in the Amyloid Precursor Protein Cytoplasmic Tail Detected by NMR, Journal of Molecular Biology 307, 871-884.

Wang, C., Xi, J., Begley, T. P. and Nicholson, L. K. (2001) Solution Structure of ThiS and Implications for the Evolutionary Roots of Ubiquitin, Nature Structural Biology, 8, 47-51.

Loh, A. P., Pawley, N. H., Nicholson, L. K. and Oswald, R. E. (2001) An increase in side chain entropy facilitates effector binding: NMR characterization of the side chain methyl group dynamics in cdc42Hs, Biochemistry 40(15), 4590-4600.

Reinking, J. L., Schatz, G. W., Vogt, V. and Nicholson, L. K. (2001) Letter to the Editor: 1H, 15N and 13C chemical shift assignments of a monomeric N-terminal deletion mutant of the Rous sarcoma virus protease, J. Biomol. NMR 19, 279-280.

Schatz, G. W., Reinking, J., Zippin, J., Nicholson, L. K. & Vogt, V. M. (2001). Importance of the N terminus of rous sarcoma virus protease for structure and enzymatic function. J Virol 75(10), 4761-70.

Pawley, N. H., Wang, C., Koide, S. and Nicholson, L. K. (2001) An Improved Method for Distinguishing Between Anisotropic Tumbling and Chemical Exchange in Analysis of 15N Relaxation Parameters, J. Biomol. NMR 20, 149-165.

Wang, C., Pawley, N. H. & Nicholson, L. K. (2001). The Role of Backbone Motions in Ligand Binding to the c-Src SH3 Domain. J. Mol. Biol. 313, 873-887.

Ramelot, T. A., Gentile, L. N. and Nicholson, L. K. (2000) Transient structure of the amyloid precursor protein cytoplasmic tail indicates preordering of structure for binding to cytosolic factors, Biochemistry, 39, 2714-2725.

Zhu, G., Xia, Y. L., Nicholson, L. K. and Sze, K. H. (2000) Protein dynamics measurements by TROSY-based NMR experiments, Journal of Magnetic Resonance, 143, 423-426.

Cordier, F., Wang, C., Grzesiek, S. and Nicholson, L. K. (2000) Ligand-induced strain in the c-Src SH3 domain detected by NMR, J. Mol. Biol. 304, 497-505.

Loh, A. P., Guo, W., Nicholson, L. K. and Oswald, R. E. (1999) Backbone dynamics of inactive, active, and effector-bound Cdc42Hs from measurements of N-15 relaxation parameters at multiple field strengths, Biochemistry, 38, 12547-12557.

Tessari, M., Gentile, L. N., Taylor, S. J., Shalloway, D. I., Nicholson, L. K. and Vuister, G. W. (1997) Heteronuclear NMR Studies of the Combined SH3-SH2 Domains of pp60c-Src: the Effects of Phosphopeptide Binding, Biochemistry, 36, 14561-14571.

Yamazaki, T., Hinck, A. C., Wang, Y.-X., Nicholson, L. K., Torchia, D. A., Wingfield, P., Stahl, S. J., Kaufman, J. D., Domaille, P. J., Hodge, C. N. and Chang, C.-H. (1996) Three Dimensional Solution Structure of the HIV-1 Protease/DMP323 Complex Determined by NMR Spectroscopy, Protein Science 5, 495-506.

Nicholson, L. K., Grzesiek, S., Yamazaki, T., Stahl, S. J., Kaufman, P. T., Wingfield, P. T., Domaille, P. J., Bax, A., and Torchia, D. A. (1995) Flexibility and Function in the HIV-1 Protease, Nature Structural Biology 2, 274-280.

Grzesiek, S., Bax, A., Nicholson, L. K., Yamazaki, T., Wingfield, P. T., Stahl, S. J., Eyermann, C. J., Torchia, D. A., Hodge, C. N., Lam, P. Y. S., Jadhav, P. K. and Chang, C.-H. (1994) NMR Evidence for the Displacement of a Conserved Interior Water Molecule by a Non-peptide Cyclic Urea Based HIV Protease Inhibitor, J. Am. Chem. Soc. 116, 1581-1582.

Yamazaki, T., Nicholson, L. K., Wingfield, P. T., Stahl, S. J., Kaufman, P. T., Domaille, P. J., Torchia, D. A. (1994) NMR and X-Ray Evidence that the HIV Protease Catalytic Aspartyl Groups Have an Essential Role in the Complex Formed by the Protease and a Non-Peptide Cyclic Urea-Based Inhibitor, J. Am. Chem. Soc. 116, 10791-10792.

Nicholson, L. K., Asakura, T., Demura, M. and Cross, T.A. (1993) A Method for Studying the Structure of Uniaxially Aligned Biopolymers Using Solid State 15N NMR: Application to Bombyx Mori Silk Fibroin Fibers Biopolymers 33, 847-861.

Nicholson, L. K., Kay, L. E., Baldisseri, D. M., Arango, J., Young, P. E., Bax, A., and Torchia, D. A. (1992) Dynamics of Methyl Groups in Proteins as Studied by Proton Detected 13C NMR Spectroscopy. Application to the Leucine Residues of Staphylococcal NucleaseBiochemistry 31, 5253-5263.

Click here to view Dr. Nicholson's PubMed listings.