Liping Yu, PhD


Contact Information

Address: NMR Core Facility, B291 CBRB, 285 Newton Road
Iowa City, IA 52242
Phone: (319) 384-3172


We are interested in molecular structure, function, dynamics, interaction, and recognition as well as metabolic profiling and drug discovery and development programs. The molecular targets could be proteins, nucleic acids, oligosaccharides, drugs/metabolites, and/or their complexes. One of the primary experimental tools used in our laboratory is NMR spectroscopy. The Carver College of Medicine NMR Core Facility has state of the art instrumentation including Bruker Avance II 800 MHz, Varian Unity Inova 600 MHz, and Bruker Avance II 500 MHz spectrometers. The Bruker 800 MHz spectrometer is equipped with a sensitive TCI cryoprobe with pulse field gradients. The Bruker 800 and 500 MHz spectrometers are also equipped with automatic tuning and matching and automatic sample exchanger, thus allowing us to run samples continuously unattended day and night. This feature is particularly valuable when screening a lot of samples, such as for sample optimization or screen a compound library for discovering novel ligands to bind to certain targets.</p>

<p>For protein structure determination, unlabeled protein could be used first by collecting simple 1D 1H NMR spectra to assess the spectral quality for suitability of NMR-based structural determination. If needed, the protein sample could be optimized by conducting simple buffer screening. Then, 15N-labeled sample is prepared, and 15N/1H HSQC spectra are collected for the samples at different solution conditions for further tuning the NMR spectral quality. If the sample is suitable for structural determination, then 15N,13C-labeled protein is prepared and a suite of backbone, side-chain, and NOESY experiments are collected for backbone, side-chain, and NOE assignments. Finally, solution structure could be calculated from NMR-derived distance and angular restraints. Depending on protein size and spectral complexity, different isotope-labeling schemes are often used for spectral simplification and sensitivity enhancement and for aiding in NMR resonance assignments.

Currently, we are working on structural determination of proteins and carbohydrate receptors involved in (1) muscular dystrophy, (2) bacterial quorum sensing, (3) microbial cell division, replication and infection, (4) Ca+2 signaling, (5) immunity receptor activation by endotoxin, (6) ubiquitin recognition by ubiquitin-binding proteins, and (7) drug characterization and development. These research projects are collaborated mainly with the faculty in the Carver College of Medicine. Many of these research targets are involved in protein-ligand interactions which are fundamentally important in cellular functions. Therefore, the research is emphasized on the understanding structurally how these proteins recognize their binding partners that could be peptide, drug, carbohydrate, or another protein, and how they perform the biological functions. We are also interested in protein modeling and intermolecular docking, e.g. by HADDOCK in order to build 3D models based on NMR and other experimental data. The Carver College of Medicine NMR Core Facility can provide the following services:

  • Consultation on NMR sample preparation
  • Assistance with experimental design
  • Assistance with NMR data collection, processing, and analyses
  • Support / assistance on molecular structural modeling and calculations
  • Providing user training / education
  • Assistance with targets that are related to drug discovery programs
  • Support for research grants and patents
  • Complete research project support (either internal or external

    Selected Publications

    Liping Yu, Brian D. Fink, Judith A. Herlein, Christine L. Oltman, Kathryn G. Lamping, and William I. Sivitz. (2014) Dietary fat, fatty acid saturation and mitochondrial bioenergetics. J. Bioenerg. Biomembr., 46, 33-44.

    Takako Yoshida-Moriguchi, Tobias Willer, Mary E. Anderson, David Venzke, Tamieka Whyte, Francesco Muntoni, Hane Lee, Stanley F. Nelson, Liping Yu, and Kevin P. Campbell. (2013) SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science, 341, 896-899.

    Natasha Pashkova, Lokesh Gakhar, Stanley C. Winistorfer, Anna B. Sunshine, Matthew Rich, Maitreya J. Dunham, Liping Yu, and Robert C. Piper. (2013) The yeast Alix homolog Bro1 functions as a ubiquitin receptor for protein sorting into multivesicular endosomes.  Developmental Cell, 25, 520-533.

    Liping Yu, Brian D. Fink, Judith A. Herlein, and William I. Sivitz. (2013) Mitochondrial function in diabetes: Novel methodology and new insight.  Diabetes, 62, 1833-1842.

    Liping Yu, Rachel L. Phillips, DeSheng Zhang, Athmane Teghanemt, Jerrold P. Weiss, and Theresa L. Gioannini. (2012) NMR studies of hexaacylated endotoxin bound to wild-type and F126A mutant MD-2 and MD-2/TLR4 ectodomain complexes.  J. Biol. Chem., 287, 16346-16355.

    Post, D. M. B.*, Yu, L.*, Krasity, B. C.* (*these authors contributed equally), Choudhury, B., Mandel, M. J., Brennan, C. A., Ruby, E. G., McFall-Ngai, M. J., Gibson, B. W., and Apicella, M. A. (2012) O-antigen and core carbohydrate of Vibrio fischeri lipopolysaccharide: composition and analysis of their role in Euprymna scolopes light organ colonization. J. Biol. Chem.,287, 8515-8530.

    Kei-ichiro, I, Yoshida-Moriguchi, T., Hara Y., Anderson, M. E., Yu, L., Campbell K. P. (2012) Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science, 335, 93-96.

    Qiu, Jiang; Yu, Liping; and Kirsch, Lee E. (2011) Estimated pKa values for specific amino acid residues in daptomycin.  J. Pharm. Sci., 100, 4225-4233.

    Feldkamp, Michael D.; Yu, Liping; and Shea, Madeline A. (2011) Structural and energetic determinants of apo calmodulin binding to the IQ-motif of the NaV1.2 voltage-dependent sodium channel. Structure, 19, 733-747.

    O'Donnell, S. E., Yu, L., Fowler, C. A., & Shea, M. A. (2011) Recognition of beta-calcineurin by the domains of calmodulin: thermodynamic and structural evidence for distinct roles. Proteins, 79, 765-786.

    Pashkova, N., Gakhar, L., Winistorfer, S. C., Yu, L., Ramaswamy, S., & Piper, R. C. (2010) WD40 repeat propellers define a ubiquitin binding domain that regulates turnover of F-box proteins. Mol. Cell, 40, 433-443.

    Feldkamp, M. D., O’Donnell, S. E., Yu, L., & Shea, M. A. (2010) Allosteric effects of the antipsychotic drug trifluoperazine on the energetics of calcium binding by calmodulin. Proteins, 78, 2265-2282.

    Barghorn, Stefan; Hillen, Heinz; Edalji, Rohinton; Barrett, Leo; Richardson, Paul; Yu, Liping; Olejniczak, Edward; Harlan, John; Holzman, Thomas. (2010) Amyloid-beta peptide analogs: oligomerization, stability, and immunogenicity. PCT Int. Appl., 233pp. WO 2010011947 A2.

    Yoshida-Moriguchi, T., Yu, L., Stalnaker, S. H., Davis, S., Kunz, S., Madson, M., Oldstone, M. B. A., Schachter, H., Wells, L., & Campbell, K. P. (2010) O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding. Science, 327, 88-92.

    Piazza, M., Yu, L., Teghanemt, A., Gioannini, T., Weiss, J., & Peri, F. (2009) Evidence of a specific interaction between new synthetic antisepsis agents and CD14. Biochemistry, 48, 12337-12344.

    Yu, L., Edalji, R., Harlan, J. E., Holzman, T. F., Pereda-Lopez, A., Labkovsky, B., Hillen, H., Barghorn, S., Ebert, U., Richardson, P., Miesbauer, L., Solomon, L., Bartley, D., Walter, K., Johnson, R. W., Hajduk, P. J., & Olejniczak, E. T. (2009) Structural characterization of a soluble amyloid beta-peptide oligomer. Biochemistry, 48, 1870-1877.

    Hillen, Heinz; Labkovsky, Boris; Olejniczak, Edward T.; Barghorn, Stefan; Holzman, Thomas F.; Harlan, John E.; Edalji, Rohinton P.; Pereda-Lopez, Ana; Yu, Liping; Ebert, Ulrich M. (2009) Methods of preparation of recombinant forms of human beta-amyloid protein and uses of these proteins. United States Patent Application, 20090214515.