Nancy Horton

Professor, Molecular and Cellular Biology
Professor, Chemistry and Biochemistry
Professor, Genetics - GIDP

My laboratory is interested in the structures and mechanisms of proteins that act upon DNA and RNA and their consequences to human health. Currently, we are investigating proteins from the human pathogen, Human Parvovirus B19, and as well as enzymes which modulate their activity using filament formation. The methods we employ include structural techniques such as x-ray crystallography, NMR and cryo-electron microscopy, and functional investigations using biochemical and high-throughput methodologies

Publications

2022

Shan, Z., N. Ghadirian, D. Lyumkis, and N. C. Horton, "Pretransition state and apo structures of the filament-forming enzyme SgrAI elucidate mechanisms of activation and substrate specificity.", J Biol Chem, vol. 298, issue 4, pp. 101760, 2022 Apr. PMCID: PMC8960973 PMID: 35202658
Lyumkis, D., and N. C. Horton, "The role of filamentation in activation and DNA sequence specificity of the sequence-specific endonuclease SgrAI.", Biochem Soc Trans, vol. 50, issue 6, pp. 1703-1714, 2022 Dec 16. PMID: 36398769
Sanchez, J. L., N. Ghadirian, and N. C. Horton, "High-Resolution Structure of the Nuclease Domain of the Human Parvovirus B19 Main Replication Protein NS1.", J Virol, vol. 96, issue 9, pp. e0216421, 2022 May 11. PMCID: PMC9093113 PMID: 35435730

2021

Townsend, J. A., H. M. Sanders, A. D. Rolland, C. K. Park, N. C. Horton, J. S. Prell, J. Wang, and M. T. Marty, "Influenza AM2 Channel Oligomerization Is Sensitive to Its Chemical Environment.", Anal Chem, vol. 93, issue 48, pp. 16273-16281, 2021 Dec 07. PMCID: PMC8665133 PMID: 34813702

2020

Park, C. K., and N. C. Horton, "Novel insights into filament-forming enzymes.", Nat Rev Mol Cell Biol, vol. 21, issue 1, pp. 1-2, 2020 01. PMID: 31676888

2019

Xu, P., S. S. Ganaie, X. Wang, Z. Wang, S. Kleiboeker, N. C. Horton, R. F. Heier, M. J. Meyers, J. E. Tavis, and J. Qiu, "Endonuclease Activity Inhibition of the NS1 Protein of Parvovirus B19 as a Novel Target for Antiviral Drug Development.", Antimicrob Agents Chemother, vol. 63, issue 3, 2019 03. PMCID: PMC6395930 PMID: 30530599
Park, C. K., and N. C. Horton, "Structures, functions, and mechanisms of filament forming enzymes: a renaissance of enzyme filamentation.", Biophys Rev, vol. 11, issue 6, pp. 927-994, 2019 Dec. PMCID: PMC6874960 PMID: 31734826
Barahona, C. J., E. L Basantes, K. J. Tompkins, D. M. Heitman, B. I. Chukwu, J. Sanchez, J. L. Sanchez, N. Ghadirian, C. K. Park, and N. C. Horton, "The Need for Speed: Run-On Oligomer Filament Formation Provides Maximum Speed with Maximum Sequestration of Activity.", J Virol, vol. 93, issue 5, 2019 03 01. PMCID: PMC6384071 PMID: 30518649
Polley, S., D. Lyumkis, and N. C. Horton, "Mechanism of Filamentation-Induced Allosteric Activation of the SgrAI Endonuclease.", Structure, vol. 27, issue 10, pp. 1497-1507.e3, 2019 10 01. PMCID: PMC6774820 PMID: 31447289

2018

Park, C. K., J. L. Sanchez, C. Barahona, E. L Basantes, J. Sanchez, C. Hernandez, and N. C. Horton, "The run-on oligomer filament enzyme mechanism of SgrAI: Part 2. Kinetic modeling of the full DNA cleavage pathway.", J Biol Chem, vol. 293, issue 38, pp. 14599-14615, 2018 09 21. PMCID: PMC6153286 PMID: 30054273

2016

Sanchez, J. L., Z. Romero, A. Quinones, K. R. Torgeson, and N. C. Horton, "DNA Binding and Cleavage by the Human Parvovirus B19 NS1 Nuclease Domain.", Biochemistry, vol. 55, issue 47, pp. 6577-6593, 2016 Nov 29. PMCID: PMC5933076 PMID: 27809499

2015

Horton, N. C., and P. A. Mathew, "NKp44 and Natural Cytotoxicity Receptors as Damage-Associated Molecular Pattern Recognition Receptors.", Front Immunol, vol. 6, pp. 31, 2015. PMCID: PMC4313717 PMID: 25699048
Shah, S., P. Dunten, A. Stiteler, C. K. Park, and N. C. Horton, "Structure and specificity of FEN-1 from Methanopyrus kandleri.", Proteins, vol. 83, issue 1, pp. 188-94, 2015 Jan. PMCID: PMC4270939 PMID: 25354467
Shah, S., J. Sanchez, A. Stewart, M. M. Piperakis, R. Cosstick, C. Nichols, C. K. Park, X. Ma, V. Wysocki, J. Bitinaite, et al., "Probing the run-on oligomer of activated SgrAI bound to DNA.", PLoS One, vol. 10, issue 4, pp. e0124783, 2015. PMCID: PMC4399878 PMID: 25880668

2013

Lyumkis, D., H. Talley, A. Stewart, S. Shah, C. K. Park, F. Tama, C. S. Potter, B. Carragher, and N. C. Horton, "Allosteric regulation of DNA cleavage and sequence-specificity through run-on oligomerization.", Structure, vol. 21, issue 10, pp. 1848-58, 2013 Oct 08. PMCID: PMC3898938 PMID: 24055317
Horton, N. C., S. O. Mathew, and P. A. Mathew, "Novel interaction between proliferating cell nuclear antigen and HLA I on the surface of tumor cells inhibits NK cell function through NKp44.", PLoS One, vol. 8, issue 3, pp. e59552, 2013. PMCID: PMC3602199 PMID: 23527218
Kim, J. R., N. C. Horton, S. O. Mathew, and P. A. Mathew, "CS1 (SLAMF7) inhibits production of proinflammatory cytokines by activated monocytes.", Inflamm Res, vol. 62, issue 8, pp. 765-72, 2013 Aug. PMID: 23695528
Ma, X., S. Shah, M. Zhou, C. K. Park, V. H. Wysocki, and N. C. Horton, "Structural analysis of activated SgrAI-DNA oligomers using ion mobility mass spectrometry.", Biochemistry, vol. 52, issue 25, pp. 4373-81, 2013 Jun 25. PMCID: PMC6402485 PMID: 23742104

2011

Aldy, K. N., N. C. Horton, P. A. Mathew, and S. O. Mathew, "2B4+ CD8+ T cells play an inhibitory role against constrained HIV epitopes.", Biochem Biophys Res Commun, vol. 405, issue 3, pp. 503-7, 2011 Feb 18. PMCID: PMC3063451 PMID: 21256826
Little, E. J., P. W. Dunten, J. Bitinaite, and N. C. Horton, "New clues in the allosteric activation of DNA cleavage by SgrAI: structures of SgrAI bound to cleaved primary-site DNA and uncleaved secondary-site DNA.", Acta Crystallogr D Biol Crystallogr, vol. 67, issue Pt 1, pp. 67-74, 2011 Jan. PMCID: PMC3016018 PMID: 21206063

2010

Park, C. K., A. P. Stiteler, S. Shah, I. M Ghare, J. Bitinaite, and N. C. Horton, "Activation of DNA cleavage by oligomerization of DNA-bound SgrAI.", Biochemistry, vol. 49, issue 41, pp. 8818-30, 2010 Oct 19. PMCID: PMC2972665 PMID: 20836535
Park, C. K., H. K. Joshi, A. Agrawal, I. M Ghare, E. J. Little, P. W. Dunten, J. Bitinaite, and N. C. Horton, "Domain swapping in allosteric modulation of DNA specificity.", PLoS Biol, vol. 8, issue 12, pp. e1000554, 2010 Dec 07. PMCID: PMC2998434 PMID: 21151881
Horton, N. C., and C. K. Park, "Crystallization of zinc finger proteins bound to DNA.", Methods Mol Biol, vol. 649, pp. 457-77, 2010. PMID: 20680852

2009

Dunten, P. W., E. J. Little, and N. C. Horton, "The restriction enzyme SgrAI: structure solution via combination of poor MIRAS and MR phases.", Acta Crystallogr D Biol Crystallogr, vol. 65, issue Pt 4, pp. 393-8, 2009 Apr. PMCID: PMC2659886 PMID: 19307723

2008

Babic, A. C., E. J. Little, V. M. Manohar, J. Bitinaite, and N. C. Horton, "DNA distortion and specificity in a sequence-specific endonuclease.", J Mol Biol, vol. 383, issue 1, pp. 186-204, 2008 Oct 31. PMCID: PMC2605692 PMID: 18762194

Pages

Supervising

Christopher Boles