Carolyn Teschke

Professor and Department Head

Molecular and Cell Biology / Structural Biology, Biochemistry and Biophysics (SB3) / Microbiology

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Education: Ph.D., Washington State University; Post-doctoral training, Massachusetts Institute of Technology

Research Interests: Our work addresses how viruses assemble capsids precisely that have the proper size and shape.  Assembly of a virus is a highly coordinated process involving sequential addition of multiple proteins, ultimately leading to an infectious virion. In the tailed phages, herpesviruses, adenoviruses, and many other dsDNA viruses, the initial product of assembly is a precursor capsid (the protein shell of a virus) known as the procapsid, which undergoes a series of reactions to become the final mature capsid.

In tailed phages, some archaeal viruses and herpesviruses, the viral capsids are assembled from coat proteins with the HK97 fold and have remarkably similar assembly pathways. Our primary model is bacteriophage P22.  We use P22 to understand the multitude of protein interactions involved in assembling a virus. These include how the portal protein is incorporated, to how scaffolding protein interacts with all of the proteins needed to assemble a procapsid, the process of capsid maturation, and how the ejection proteins work. Another question we are evaluating is how evolution has changed the way the capsid proteins function with one another by comparing the capsid interactions in similar but distantly related phages, or even between P22 and herpesvirus.

Selected Publications:

Whitehead, R. D. III, Teschke, C.M., & Alexandrescu, A.T (2022) “Pulse-field gradient nuclear magnetic resonance of protein translational diffusion from native to non-native states”, Protein Sci, in press. https://doi.org/10.1002/pro.4321

Asija, K, Teschke, C.M. (2019) A hydrophobic network: Intersubunit and intercapsomer interactions stabilizing the bacteriophage P22 capsid. J. Virology, in press May 8. pii: JVI.00727-19. doi: 10.1128/JVI.00727-19.

Dedeo C., Cingolani, G., Teschke C.M. (2019) Portal protein: the orchestrator of capsid assembly for the dsDNA tailed bacteriophages and herpesviruses. Annual Reviews of Virology, in press.

Asija, K., Teschke C.M. (2019) Of capsid structure and stability: the partnership between charged residues of E-loop and P-domain of the bacteriophage P22 coat protein. Virology. 534:45-53. doi: 10.1016/j.virol.2019.05.021.

Newcomer, R.L., Schrad, J.R., Gilcrease, E.B., Casjens, S.R., Feig, M., Teschke, C.M.*, Alexandrescu, A.T., and Parent, K.N* (2019) The phage L capsid decoration protein has a novel OB-fold and an unusual capsid binding strategy. Elife. 8:e45345. doi: 10.7554/eLife.45345. *co-corresponding authors

Duda, R.L., Teschke, C.M. (2019) The amazing HK97 fold: versatile results of modest differences. Curr. Opin. Virol., 36:9-16, doi: 10.1016/j.coviro.2019.02.001.

Motwani, T., Teschke, C.M. (2019). The architect of virus assembly: portal protein nucleates procapsid assembly in bacteriophage P22. J. Virology, 93:e00187-19. doi: 0.1128/JVI.00187-19. Selected by editors for a JVi Spotlight.

Tripler, T.N. Kaplan, A.R., Alexandrescu, A.T.*, and Teschke, C.M.* (2019) Conservation and divergence of the I-domain inserted into the ubiquitous HK97 coat protein fold in the P22-like bacteriophages. J. Virology, 93:e00007-19. doi:10.1128/JVI.00007-19. *co-corresponding authors

Newcomer, R.L., Belato, H., Teschke, C.M.*, Alexandrescu, A.A.* (2018) NMR assignments of Decorator, a phage-cementing 43 kDa homotrimer, Biomol. NMR Assignments, 12:339-343. doi: 10.1007/s12104-018-9836-1.  *co-corresponding authors

Asija K, Teschke CM. 2018. Lessons from bacteriophages part 1: Deriving utility from protein structure, function, and evolution. PLoS Pathog. DOI: 10.1371/journal.ppat.1006971

Asija K, Teschke CM. 2018. Lessons from bacteriophages part 2: A saga of scientific breakthroughs and prospects for their use in human health. PLoS Pathog. DOI: 10.1371/journal.ppat.1006970

Tina Motwani, Ravi K. Lokareddy, Carmen A. Dunbar, Juliana R. Cortines, Martin F. Jarrold, Gino Cingolani, Carolyn M. Teschke (2017) A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly. Science Advances DOI: 10.1126/sciadv.1700423.

Lokareddy, R., Sankhala, R., Roy, A., Afonine, P., Motwani, T., Teschke, C.M., Parent, K.N., and Cingolani, G. (2017) Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation. Nature Communications, 8:14310. doi: 10.1038/ncomms14310.

Tripler, T.N., Teschke, C.M.*, Alexandrescu, A.T.* (2017) NMR assignments for the insertion domain of bacteriophage Sf6 coat protein. Biomol. NMR Assignments, 11:35-38. doi: 10.1007/s12104-016-9716-5. Epub 2016 Oct 31. *co-corresponding authors

Wu, W., Leavitt, J.C., Cheng N., Gilcrease, E.B., Motwani, T., Teschke, C.M., Casjens, S.R., Steven, A.C. (2016) Localization of the Houdinisome (Ejection Proteins) inside the Bacteriophage P22 Virion by Bubblegram Imaging. MBio, 7(4). pii: e01152-16. doi: 10.1128/mBio.01152-16.

Keifer, D.Z., Motwani, T., Teschke, C.M., Jarrold, M.F. (2016) Measurement of the accurate mass of a 50 MDa infectious virus. Rapid Commun. Mass Spectrom., 30:1957-62. doi: 10.1002/rcm.7673.

Keifer, D.Z., Motwani, T., Teschke, C.M., Jarrold, M.F. (2016) Acquiring Structural Information on Virus Particles with Charge Detection Mass Spectrometry. J. Amer. Soc. for Mass Spec., 27,1028-36. doi: 10.1007/s13361-016-1362-8

Harprecht, C, Okifo, O, Robbins, K.J., Motwani, T., Alexandrescu, A.T., Teschke, C.M. (2016) Contextual Role of a Salt-Bridge in the Phage P22 Coat Protein I-Domain. J Biol Chem.; 291:11359-72. doi: 10.1074/jbc.M116.716910

Newcomer, R., Fraser, L., Teschke, C.M.*, Alexandrescu, A.T.* (2015) Mechanism of protein denaturation: partial unfolding of the P22 coat protein I-domain by urea binding. Biophysical J., 109, 2666-77.  *co-corresponding authors

D’Lima, N.G., Teschke, C.M. (2015) A molecular staple: D-loops in the I-domain of bacteriophage P22 coat protein make important inter-capsomer contacts required for procapsid assembly. J. Virol., 89, 10569-79. doi: 10.1128/JVI.01629-15

D’Lima, N.G., Teschke, C.M. (2015) A method to investigate protein association with intact sealed Mycobacterial membrane vesicles. Analytical Biochemistry, 485, 109-111. doi: 10.1016/j.ab.2015.06.023

Tripler, T.N., Maciejewski, M.W., Teschke, C.M.*, Alexandrescu, A.T.* (2015) NMR assignments for the insertion domain of bacteriophage CUS-3 coat protein, Biomol. NMR Assignments, 9, 333-6. doi: 10.1007/s12104-015-9604-4. *co-corresponding authors

Suhanovsky, M., Teschke, C. (2015) Nature׳s favorite building block: Deciphering folding and capsid assembly of proteins with the HK97-fold. Virology doi:10.1016/j.virol.2015.02.055.

Rizzo, A.A., Suhanovsky, M.M., Baker, M.L., Fraser, L.C.R., Jones, L.M., Rempel, D.L., Gross, M.L., Chiu, W., Alexandrescu, A.T. & Teschke, C.M. (2014) “Multiple functional roles of the accessory I-domain of bacteriophage P22 coat protein revealed by NMR structure and cryoEM modeling”. Structure 22, 830-841.

Cortines JR, Motwani T, Vyas AA, Teschke CMJ Virol. (2014) Highly specific salt bridges govern bacteriophage P22 icosahedral capsid assembly: identification of the site in coat protein responsible for interaction with scaffolding protein. May;88(10):5287-97. doi: 10.1128/JVI.00036-14. Epub 2014 Mar 5.

Padilla-Meier GP, Gilcrease EB, Weigele PR, Cortines JR, Siegel M, Leavitt JC, Teschke CM, Casjens SR (2012) Unraveling the Role of the C-terminal Helix-Turn-Helix of the Coat-binding Domain of Bacteriophage P22 Scaffolding Protein. J Biol Chem. 2012 Aug 9. [Epub ahead of print]

Teschke CM. (2012) Themes and variations of viral small terminase proteins. Structure 20(8): 1291-2.

Parent KN, Deedas CT, Egelman EH, Casjens SR, Baker TS, Teschke CM (2012) Stepwise molecular display utilizing icosahedral and helical complexes of phage coat and decoration proteins in the development of robust nanoscale display vehicles. Biomaterials 33(22):5628-37. Epub 2012 May 8.

Zlotnick A, Suhanovsky MM, Teschke CM (2012) The energetic contributions of scaffolding and coat proteins to the assembly of bacteriophage procapsids. Virology428(1):64-9. Epub 2012 Apr 20

Cortines JR, Weigele PR, Gilcrease EB, Casjens SR, Teschke CM (2011) Decoding bacteriophage P22 assembly: identification of two charged residues in scaffolding protein responsible for coat protein interaction. Virology 421(1):1-11. Epub 2011 Oct 4

Suhanovsky MM, Teschke CM (2011) Bacteriophage P22 capsid size determination: roles for the coat protein telokin-like domain and the scaffolding protein amino-terminus.
Virology 417(2):418-29. Epub 2011 Jul 23.

Padilla-Meier GP, Teschke CM (2011) Conformational changes in bacteriophage P22 scaffolding protein induced by interaction with coat protein. J Mol Biol 410(2):226-40. Epub 2011 May 14.

Parent KN, Sinkovits RS, Suhanovsky MM, Teschke CM, Egelman EH, Baker TS. (2010) Cryo-reconstructions of P22 polyheads suggest that phage assembly is nucleated by trimeric interactions among coat proteins.Phys Biol. 7(4):045004

Suhanovsky MM, Parent KN, Dunn SE, Baker TS, Teschke CM (2010) Determinants of bacteriophage P22 polyhead formation: the role of coat protein flexibility in conformational switching.Mol Microbiol 77(6):1568-82 Epub 2010 Aug 18

Teschke CM, Parent KN (2010) Let the phage do the work: using the phage P22 coat protein structures as a framework to understand its folding and assembly mutants. Virology 401(2):119-30. Epub 2010 Mar 16.

Parent KN, Khayat R, Tu LH, Suhanovsky MM, Cortines JR, Teschke CM, Johnson JE, Baker TS (2010) P22 coat protein structures reveal a novel mechanism for capsid maturation: stability without auxiliary proteins or chemical crosslinks. Structure 18(3):390-401

Parent KN, Khayat R, Tu LH, Suhanovsky MM, Cortines JR, Teschke CM, Johnson JE, Baker TS. P22 coat protein structures reveal a novel mechanism for capsid maturation: stability without auxiliary proteins or chemical crosslinks. Structure. 2010 Mar 10;18(3):390-401

Hou, J.M., D’Lima, N.G., Rigel, R.W., Gibbons, H.S., Braunstein, M., Teschke, C.M. (2008) ATPase activity of Mycobacterium tuberculosis SecA1 and SecA2 proteins and its importance to SecA2 function in macrophages. J. Bacteriol., 190, 4880-7.

Parent, K.N., Suhanovsky, M.M., Teschke, C.M. (2007) Polyhead formation in phage P22 pinpoints a region in coat protein required for conformational switching. Molecular Microbiol. 65,1300-10.

Parent, K.N., Teschke, C.M. (2007) GroEL/S substrate specificity based on substrate unfolding propensity. Cell Stress and Chaperones, 12, 20-32.

Parent, K.N., Suhanovsky, M.M., Teschke, C.M. (2007) Phage P22 procapsids equilibrate with free coat protein subunits. J. Mol. Biol., 365, 513-22.

Parent 4. K.N., Zlotnick, A., Teschke, C.M. (2006) Quantitative analysis of multi-component spherical virus assembly: Scaffolding protein contributes to the global stability of phage P22 procapsids. J. Mol. Biol., 359,1097-106.