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Ernesto Fuentes, PhD

Associate Professor of Biochemistry

Contact Information

4-632 Bowen Science Building (BSB)
Iowa City, IA 52242



BChE, Chemical Engineering, University of Dayton
MS, Biology, University of Dayton
PhD, Biochemistry, University of Illinois
Postdoctoral Fellow, Structural Biology, University of Pennsylvania
Postdoctoral Fellow, Structural and Cancer Biology, University of North Carolina

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Molecular Medicine, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center for Biocatalysis and Bioprocessing, Holden Comprehensive Cancer Center

Research Summary

Research in my laboratory focuses on important problems in signal transduction pertinent to human health. Our approach is interdisciplinary, combining, biochemical, biophysical, cell biological and molecular biology methods to gain insight into the mechanisms governing signal transduction in eukaryotic and prokaryotic systems. The major goal is to elucidate the molecular mechanisms that regulate signal transduction. Our recent work has focused on two systems.

The first system involves the Rho family of GTPases, a subfamily of the well known Ras superfamily. In their active state, Rho GTPases interact with effector proteins to coordinate changes in gene expression and the actin cytoskeleton. Several molecules, including guanine exchange factors (GEFs), regulate the active state of Rho GTPases. Importantly, the aberrant function of GEFs has been associated with developmental anomalies, mental retardation, and human disease. The long-term goal of this research is to understand the detailed molecular mechanism(s) by which GEF proteins regulate the activation of Rho-family GTPases and how their deregulation leads to disease.

The second system centers on bacterial chemosensory in the soil bacterium Myxococcus xanthus. Chemosensory in Myxococcus xanthus is essential for developmental gene expression, biofilm formation, intercellular communication and gliding motility. In collaboration with Dr. John Kirby (U of I, Microbiology) we are elucidating the biochemical and structural basis for Myxococcus xanthus chemosensory signaling.


Opuu, V., Sun, Y. J., Panel, N., Fuentes, E. J. & Simonson, T. (2020). A physics-based energy function allows the computational redesign of a PDZ domain. (Vols. 10). (1), pp. 111150. Sci Rep.. PMID: 32636412.

Tiwari, N., Lopez-Redondo, M., Miguel-Romero, L., Kulhankova, K., Cahill, M. P., Tran, P. M., Kinney, K. J., Kilgore, S. H., Al-Tameemi, H., Herfst, C. A., Tuffs, S. W., Kirby, J. R., Boyd, J. M., McCormick, J. K., Salgado-Pabon, W., Marina, A., Schlievert, P. M. & Fuentes, E. J. (2020). The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines. Proc Natl Acad Sci U S A, 117(20), 10989-10999. PMID: 32354997.

Crosby, H. A., Tiwari, N., Kwiecinski, J. M., Xu, Z., Dykstra, A., Jenul, C., Fuentes, E. J. & Horswill, A. R. (2020). The Staphylococcus aureus ArlRS two-component system regulates virulence factor expression through MgrA. Mol Microbiol, 113(1), 103-122. PMID: 31618469.

Liu, X., Golden, L., Lopez, J., Shepher, T., Yu, L. & Fuentes, E. (2019). Conformational Dynamics and Cooperativity Drive the Specificity of a Protein-Ligand Interaction. Biophys J, 116(12), 2314-2330. PMID: 31146922.

Liu, X., Fuentes, E. (2019). Emerging themes in PDZ domain signaling: Structure, function and inhibition. Int Rev Cell Mol Biol., 343, 1-90.

Awadia, S., Huq, F., Arnold, T., Goicoechea, S., Sun, Y., Hou, T., Kreider-Letterman, G., Massimi, P., Banks, L., Fuentes, E., Miller, A. & Garia-Mata, R. (2019). SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility. Journal of Cell Biology, 218(8), 2699-2725. PMID: 31248911.

Panel, N., Villa, F., Fuentes, E. J. & Simonson, T. (2018). Accurate PDZ: peptide binding specificity with additive and polarizable free energy simulations. Biophysical Journal, 114(5), 1091-1102. PMID: 29539396.

Xu, Z., Gakhar, L., Bain, F. E., Spies, M. & Fuentes, E. J. (2017). The Tiam1 guanine nucleotide exchange factor is auto-inhibited by its pleckstrin homology coiled-coil extension domain. The Journal of biological chemistry, 292(43), 17777-17793. PMID: 28882897.

Panel, N., Sun, Y. J., Fuentes, E. J. & Simonson, T. (2017). A Simple PB/LIE Free Energy Function Accurately Predicts the Peptide Binding Specificity of the Tiam1 PDZ Domain. Frontiers in molecular biosciences, 4, 65. PMID: 29018806.

Mignon, D., Panel, N., Chen, X., Fuentes, E. J. & Simonson, T. (2017). Computational Design of the Tiam1 PDZ Domain and Its Ligand Binding. Journal of chemical theory and computation, 13(5), 2271-2289. PMID: 28394603.

Liu, X., Speckhard, D. C., Shepherd, T. R., Sun, Y. J., Hengel, S. R., Yu, L., Fowler, C. A., Gakhar, L. & Fuentes, E. J. (2016). Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions. Structure (London, England : 1993), 24(12), 2053-2066. PMID: 27998539.

Darnell, C., Wilson, J., Tiwari, N., Fuentes, E. & Kirby, J. (2014). Chemosensory regulation of a HEAT-repeat protein couples aggregation and sporulation in Myxococcus xanthus. J Bacteriol, 196(17), 3160-8. PMID: 24957622.

Willett, J. W., Tiwari, N., Muller, S., Hummels, K. R., Houtman, J. C., Fuentes, E. J. & Kirby, J. R. (2013). Specificity residues determine binding affinity for two-component signal transduction systems. MBio, 4(6), e00420-13. PMID: 24194534.

Joshi, M., Gakhar, L. & Fuentes, E. J. (2013). High-resolution structure of the Tiam1 PHn-CC-Ex domain. Acta crystallographica. Section F, Structural biology and crystallization communications, 69(Pt 7), 744-52. PMID: 23832200.

Liu, Y., Collins, C., Kiosses, W. B., Murray, A. M., Joshi, M., Shepherd, T. R., Fuentes, E. J. & Tzima, E. (2013). A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. The Journal of cell biology, 201(6), 863-73. PMID: 23733346.

Liu, X., Shepherd, T. R., Murray, A. M., Xu, Z. & Fuentes, E. J. (2013). The structure of the Tiam1 PDZ domain/ phospho-syndecan1 complex reveals a ligand conformation that modulates protein dynamics. Structure (London, England : 1993), 21(3), 342-54. PMID: 23395182.

(2013). The Liu et al. manuscript (publication #22) was published in the March 2013 issue of Structure as the cover article. (Vols. 21). pp. 1-13. Structure.

Shepherd, T. R., Hard, R. L., Murray, A. M., Pei, D. & Fuentes, E. J. (2011). Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains. Biochemistry, 50(8), 1296-308. PMID: 21192692.

Shepherd, T. R., Fuentes, E. J. (2011). Structural and thermodynamic analysis of PDZ-ligand interactions. Methods in enzymology, 488, 81-100. PMID: 21195225.

Wen, H., Kim, N., Fuentes, E. J., Mallinger, A., Gonzalez-Alegre, P. & Glenn, K. A. (2010). FBG1 is a promiscuous ubiquitin ligase that sequesters APC2 and causes S-phase arrest. Cell cycle (Georgetown, Tex.), 9(22), 4506-17. PMID: 21135578.

Ramadugu, S. K., Chung, Y. H., Fuentes, E. J., Rice, K. G. & Margulis, C. J. (2010). In silico prediction of the 3D structure of trimeric asialoglycoprotein receptor bound to triantennary oligosaccharide. Journal of the American Chemical Society, 132(26), 9087-95. PMID: 20540518.

Shepherd, T. R., Klaus, S. M., Liu, X., Ramaswamy, S., DeMali, K. A. & Fuentes, E. J. (2010). The Tiam1 PDZ domain couples to Syndecan1 and promotes cell-matrix adhesion. Journal of molecular biology, 398(5), 730-46. PMID: 20361982.

Petit, C. M., Zhang, J., Sapienza, P. J., Fuentes, E. J. & Lee, A. L. (2009). Hidden dynamic allostery in a PDZ domain. Proceedings of the National Academy of Sciences of the United States of America, 106(43), 18249-54. PMID: 19828436.

Law, A. B., Fuentes, E. J. & Lee, A. L. (2009). Conservation of side-chain dynamics within a protein family. Journal of the American Chemical Society, 131(18), 6322-3. PMID: 19374353.

Fuentes, E. J., Gilmore, S. A., Mauldin, R. V. & Lee, A. L. (2006). Evaluation of energetic and dynamic coupling networks in a PDZ domain protein. Journal of molecular biology, 364(3), 337-51. PMID: 17011581.

Tsonis, P. A., Fuentes, E. J. (2006). Focus on molecules: Pax-6, the eye master. Experimental eye research, 83(2), 233-4. PMID: 16563385.

Fuentes, E. J., Der, C. J. & Lee, A. L. (2004). Ligand-dependent dynamics and intramolecular signaling in a PDZ domain. Journal of molecular biology, 335(4), 1105-15. PMID: 14698303.

Fuentes, E. J., Karnoub, A. E., Booden, M. A., Der, C. J. & Campbell, S. L. (2003). Critical role of the pleckstrin homology domain in Dbs signaling and growth regulation. The Journal of biological chemistry, 278(23), 21188-96. PMID: 12637530.

Dai, Q. H., Tommos, C., Fuentes, E. J., Blomberg, M. R., Dutton, P. L. & Wand, A. J. (2002). Structure of a de novo designed protein model of radical enzymes. Journal of the American Chemical Society, 124(37), 10952-3. PMID: 12224922.

Kranz, J. K., Flynn, P. F., Fuentes, E. J. & Wand, A. J. (2002). Dissection of the pathway of molecular recognition by calmodulin. Biochemistry, 41(8), 2599-608. PMID: 11851407.

Liu, W., Flynn, P. F., Fuentes, E. J., Kranz, J. K., McCormick, M. & Wand, A. J. (2001). Main chain and side chain dynamics of oxidized flavodoxin from Cyanobacterium anabaena. Biochemistry, 40(49), 14744-53. PMID: 11732893.

Gibney, B. R., Huang, S. S., Skalicky, J. J., Fuentes, E. J., Wand, A. J. & Dutton, P. L. (2001). Hydrophobic modulation of heme properties in heme protein maquettes. Biochemistry, 40(35), 10550-61. PMID: 11523997.

Fuentes, E. J., Wand, A. J. (1998). Local stability and dynamics of apocytochrome b562 examined by the dependence of hydrogen exchange on hydrostatic pressure. Biochemistry, 37(28), 9877-83. PMID: 9665691.

Fuentes, E. J., Wand, A. J. (1998). Local dynamics and stability of apocytochrome b562 examined by hydrogen exchange. Biochemistry, 37(11), 3687-98. PMID: 9521687.

Qi, P. X., Fuentes, E. J., Beckman, R. A., Di Stefano, D. L. & Wand, A. J. (1995). Solution Structures of horse ferro- and ferricytochrome c using 2D and 3D 1H NMR and restrained simulated annealing. Techniques in Protein Chemistry VI, 8th, 511-519.

Qi, P. X., Urbauer, J. L., Fuentes, E. J., Leopold, M. F. & Wand, A. J. (1994). Structural water in oxidized and reduced horse heart cytochrome c. Nature structural biology, 1(6), 378-82. PMID: 7664051.

Fuentes, E. J., Pachter, R. & Tsonis, P. A. (1994). On the three-dimensional structure of the Hydra head activator neuropeptide. In vivo (Athens, Greece), 8(2), 199-205. PMID: 7919122.

Fuentes, E. J., Mescher, A. L., Ekman, R. & Tsonis, P. A. (1993). Expression of hydra head activator in newt tissues and effects on limb regeneration. In vivo (Athens, Greece), 7(1), 59-63. PMID: 8389215.