Exploring the different states of wild-type T-cell receptor and mutant conformational changes towards understanding the antigen recognition

References

• Alvarez-Navarro, C., Cragnolini, J. J., Dos Santos, H. G., Barnea, E., Admon, A., Morreale, A., & López de Castro, J. A. (2013). Novel HLA-B27-restricted epitopes from Chlamydia trachomatis generated upon endogenous processing of bacterial proteins suggest a role of molecular mimicry in reactive arthritis. Journal of Biological Chemistry, 288(36), 25810–25825. doi:10.1074/jbc.M113.493247
   PubMed Web of Science ®Google Scholar
• Armstrong, K. M., Insaidoo, F. K., & Baker, B. M. (2008a). Thermodynamics of T cell receptor-peptide/MHC interactions: Progress and opportunities. Journal of Molecular Recognition, 21(4), 275–287. doi:10.1002/jmr.896
   PubMed Web of Science ®Google Scholar
• Armstrong, K. M., Piepenbrink, K. H., & Baker, B. M. (2008b). Conformational changes and flexibility in T-cell receptor recognition of peptide-MHC complexes. Biochemical Journal, 415(2), 183–196. doi:10.1042/BJ20080850
   PubMedGoogle Scholar
• Ayres, C. M., Scott, D. R., Corcelli, S. A., & Baker, B. M. (2016). Differential utilization of binding loop flexibility in T cell receptor ligand selection and cross-reactivity. Scientific Reports, 6(1), 25070. doi:10.1038/srep25070
   PubMedGoogle Scholar
• Bahar, I., Chennubhotla, C., & Dror, T. (2007). Intrinsic enzyme dynamics in the unbound state and relation to allosteric regulation. Current Opinion in Structural Biology, 17(6), 633–640. doi:10.1016/j.sbi.2007.09.011
   PubMed Web of Science ®Google Scholar
• Baker, B. M., Scott, D. R., Blevins, S. J., & Hawse, W. F. (2012). Structural and dynamic control of T-cell receptor specificity, cross-reactivity, and binding mechanism. Immunological Reviews, 250(1), 10–31. doi:10.1111/j.1600-065X.2012.01165.x
   PubMedGoogle Scholar
• Berman, H. M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T. N., Weissig, H., … Bourne, P. E. (2000). The protein data bank. Nucleic Acids Research, 28(1), 235–242. doi:10.1093/nar/28.1.235
   PubMed Web of Science ®Google Scholar
• Boehr, D. D., Nussinov, R., & Wright, P. E. (2009). The role of dynamic conformational ensembles in biomolecular recognition. Nature Chemical Biology, 5(11), 789–796. doi:10.1038/nchembio.232
   PubMed Web of Science ®Google Scholar
• Boniface, J. J., Reich, Z., Lyons, D. S., & Davis, M. M. (1999). Thermodynamics of T cell receptor binding to peptide-MHC: Evidence for a general mechanism of molecular scanning. Proceedings of the National Academy of Sciences USA, 96(20), 11446–11451. doi:10.1073/pnas.96.20.11446
   PubMed Web of Science ®Google Scholar
• Brylinski, M., & Skolnick, J. (2007). What is the relationship between the global structures of apo and holo proteins? Proteins: Structure, Function, and Bioinformatics, 70(2), 363–377. doi:10.1002/prot.21510
   Web of Science ®Google Scholar
• Case, D. A., Babin, V., Berryman, J. T., Betz, R. M., Cai, Q., Cerutti, D. S., … Kollman, P. A. (2014). AMBER 14. San Francisco: University of California.
   Google Scholar
• Chen, J.-L., Stewart-Jones, G., Bossi, G., Lissin, N. M., Wooldridge, L., Choi, E. M. L., … Cerundolo, V. (2005). Structural and kinetic basis for heightened immunogenicity of T cell vaccines. The Journal of Experimental Medicine, 201(8), 1243–1255. doi:10.1084/jem.20042323
   PubMed Web of Science ®Google Scholar
• Chlewicki, L. K., Holler, P. D., Monti, B. C., Clutter, M. R., & Kranz, D. M. (2005). High-affinity, peptide-specific T cell receptors can be generated by mutations in CDR1, CDR2 or CDR3. Journal of Molecular Biology, 346(1), 223–239. doi:10.1016/j.jmb.2004.11.057
   PubMed Web of Science ®Google Scholar
• Csermely, P., Palotai, R., & Nussinov, R. (2010). Induced fit, conformational selection and independent dynamic segments: An extended view of binding events. Trends in Biochemical Sciences, 35(10), 539–546. doi:10.1016/j.tibs.2010.04.009
   PubMed Web of Science ®Google Scholar
• Cuendet, M. A., Zoete, V., & Michielin, O. (2011). How T cell receptors interact with peptide-MHCs: A multiple steered molecular dynamics study. Proteins: Structure, Function, and Bioinformatics, 79(11), 3007–3024. doi:10.1002/prot.23104
   PubMed Web of Science ®Google Scholar
• Dill, K. A., & Chan, H. S. (1997). From Levinthal to pathways to funnels. Nature Structural Biology, 4(1), 10–19. doi:10.1038/nsb0197-10
   PubMedGoogle Scholar
• Durrant, J. D., & McCammon, J. A. (2011). Molecular dynamics simulations and drug discovery. BMC Biology, 9, 71. doi:10.1186/1741-7007-9-71
   PubMed Web of Science ®Google Scholar
• Essmann, U., Perera, L., Berkowitz, M. L., Darden, T., Lee, H., & Pedersen, L. G. (1995). A smooth particle meshes Ewald method. The Journal of Chemical Physics, 103(19), 8577–8593. doi:10.1063/1.470117
   Web of Science ®Google Scholar
• Garcia, K. C., Degano, M., Pease, L. R., Huang, M., Peterson, P. A., Teyton, L., & Wilson, I. A. (1998). Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science, 279(5354), 1166–1172. doi:10.1126/science.279.5354.1166
   PubMed Web of Science ®Google Scholar
• Garcia, K. C., Degano, M., Stanfield, R. L., Brunmark, A., Jackson, M. R., Peterson, P. A., … Wilson, I. A. (1996). An αβ T Cell Receptor Structure at 2.5 Å and its orientation in the TCR-MHC complex. Science, 274(5285), 209–219. doi:10.1126/science.274.5285.209
   PubMed Web of Science ®Google Scholar
• Gaud, G., Lesourne, R., & Love, P. E. (2018). Regulatory mechanisms in T cell receptor signalling. Nature Reviews Immunology, 18(8), 485–497. doi:10.1038/s41577-018-0020-8
   PubMed Web of Science ®Google Scholar
• Gerstein, M., & Krebs, W. (1998). A database of macromolecular motions. Nucleic Acids Research, 26(18), 4280–4290. doi:10.1093/nar/26.18.4280
   PubMed Web of Science ®Google Scholar
• Gill, J., Jayaswal, P., & Salunke, D. M. (2014). Antigen exposure leads to rigidification of germline antibody combining site. Journal of Bioinformatics and Computational Biology, 12(3), 1450006. doi:10.1142/S0219720014500061
   PubMed Web of Science ®Google Scholar
• Gohlke, H., & Case, D. A. (2004). Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf. Journal of Computational Chemistry, 25(2), 238–250. doi:10.1002/jcc.10379
   PubMed Web of Science ®Google Scholar
• Gutteridge, A., & Thornton, J. (2004). Conformational change in substrate binding, catalysis and product release: An open and shut case? FEBS Letters, 567(1), 67–73. doi:10.1016/S0014-5793(04)00364-3
   PubMed Web of Science ®Google Scholar
• Haidar, J. N., Pierce, B., Yu, Y., Tong, W., Li, M., & Weng, Z. (2009). Structure-based design of a T-cell receptor leads to nearly 100-fold improvement in binding affinity for pepMHC. Proteins: Structure, Function, and Bioinformatics, 74(4), 948–960. doi:10.1002/prot.22203
   PubMed Web of Science ®Google Scholar
• Hare, B. J., Wyss, D. F., Osburne, M. S., Kern, P. S., Reinherz, E. L., & Wagner, G. (1999). Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor. Nature Structural Biology, 6(6), 574–581. [Mismatch] doi:10.1038/9359
   PubMedGoogle Scholar
• Hoffmann, T., Krackhardt, A. M., & Antes, I. (2015). Quantitative analysis of the association angle between T-cell Receptor Vα/Vβ domains reveals important features for epitope recognition. PLoS Computational Biology, 11(7), e1004244. doi:10.1371/journal.pcbi.1004244
   PubMed Web of Science ®Google Scholar
• Holler, P. D., & Kranz, D. M. (2004). T cell receptors: Affinities, cross-reactivities, and a conformer model. Molecular Immunology, 40(14–15), 1027–1031. doi:10.1016/j.molimm.2003.11.013
   PubMed Web of Science ®Google Scholar
• Holler, P. D., Chlewicki, L. K., & Kranz, D. M. (2003). TCRs with high affinity for foreign pMHC show self-reactivity. Nature Immunology, 4(1), 55–62. doi:10.1038/ni863
   PubMed Web of Science ®Google Scholar
• Humphrey, W., Dalke, A., & Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33–38. doi:10.1016/0263-7855(96)00018-5
   PubMedGoogle Scholar
• Ishizuka, J., Stewart-Jones, G. B., van der Merwe, A., Bell, J. I., McMichael, A. J., & Jones, E. Y. (2008). The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain. Immunity, 28(2), 171–182.
   PubMed Web of Science ®Google Scholar
• Jones, L. L., Colf, L. A., Stone, J. D., Garcia, K. C., & Kranz, D. M. (2008). Distinct CDR3 conformations in TCRs determine the level of cross-reactivity for diverse antigens, but not the docking orientation. The Journal of Immunology, 181(9), 6255–6264. doi:10.4049/jimmunol.181.9.6255
   PubMed Web of Science ®Google Scholar
• Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W., & Klein, M. L. (1983). Comparison of simple potential functions for simulating liquid water. The Journal of Chemical Physics, 79(2), 926–935. doi:10.1063/1.445869
   Web of Science ®Google Scholar
• Karplus, M., & McCammon, J. A. (2002). Molecular dynamics simulations of biomolecules. Nature Structural Biology, 9(9), 646–652. doi:10.1038/nsb0902-646
   PubMedGoogle Scholar
• Knapp, B., & Deane, C. M. (2016). T-Cell receptor binding affects the dynamics of the Peptide/MHC-I complex. Journal of Chemical Information and Modeling, 56(1), 46–53. doi:10.1021/acs.jcim.5b00511
   PubMed Web of Science ®Google Scholar
• Knapp, B., Demharter, S., Esmaielbeiki, R., & Deane, C. M. (2015). Current status and future challenges in T-cell receptor/peptide/MHC molecular dynamics simulations. Briefings in Bioinformatics, 16(6), 1035–1044. doi:10.1093/bib/bbv005
   PubMed Web of Science ®Google Scholar
• Knapp, B., Dorffner, G., & Schreiner, W. (2013). Early relaxation dynamics in the LC 13 T cell receptor in reaction to 172 altered peptide ligands: A molecular dynamics simulation study. PLoS One, 8(6), e64464. doi:10.1371/journal.pone.0064464
   PubMed Web of Science ®Google Scholar
• Knapp, B., Dunbar, J., Alcala, M., & Deane, C. M. (2017). Variable regions of antibodies and T-Cell receptors may not be sufficient in molecular simulations investigating binding. Journal of Chemical Theory and Computation, 13(7), 3097–3105. doi:10.1021/acs.jctc.7b00080
   PubMed Web of Science ®Google Scholar
• Knapp, B., Dunbar, J., & Deane, C. M. (2014). Large scale characterization of the LC13 TCR and HLA-B8 structural landscape in reaction to 172 altered peptide ligands: A molecular dynamics simulation study. PLoS Computational Biology, 10(8), e1003748. doi:10.1371/journal.pcbi.1003748
   PubMed Web of Science ®Google Scholar
• Knapp, B., Omasits, U., Bohle, B., Maillere, B., Ebner, C., Schreiner, W., & Jahn-Schmid, B. (2009). 3-Layer-based analysis of peptide-MHC interaction: In silico prediction, peptide binding affinity and T cell activation in a relevant allergen-specific model. Molecular Immunology, 46(8–9), 1839–1844. doi:10.1016/j.molimm.2009.01.009
   PubMed Web of Science ®Google Scholar
• Knapp, B., Omasits, U., Schreiner, W., & Epstein, M. M. (2010). A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses. PLoS One, 5(7), e11653. doi:10.1371/journal.pone.0011653
   PubMed Web of Science ®Google Scholar
• Kollman, P. A., Massova, I., Reyes, C., Kuhn, B., Huo, S., Chong, L. … (2000). Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Accounts of Chemical Research, 33(12), 889–897. doi:10.1021/ar000033j
   PubMed Web of Science ®Google Scholar
• Laugel, B., Boulter, J. M., Lissin, N., Vuidepot, A., Li, Y., Gostick, E., … Sewell, A. K. (2005). Design of soluble recombinant T cell receptors for antigen targeting and T cell inhibition. Journal of Biological Chemistry, 280(3), 1882–1892. doi:10.1074/jbc.M409427200
   PubMed Web of Science ®Google Scholar
• Lees, W. D., Stejskal, L., Moss, D. S., & Shepherd, A. J. (2017). Investigating substitutions in antibody–antigen complexes using molecular dynamics: A case study with broad-spectrum, influenza a antibodies. Frontiers in Immunology, 8, 143. doi:10.3389/fimmu.2017.00143
   PubMed Web of Science ®Google Scholar
• Lefranc, M.-P., Giudicelli, V., Ginestoux, C., Jabado-Michaloud, J., Folch, G., Bellahcene, F., … Duroux, P. (2009). IMGT, the international ImMunoGeneTics information system. Nucleic Acids Research, 37(Database), D1006–D1012. doi:10.1093/nar/gkn838
   PubMedGoogle Scholar
• Levy, Y., Cho, S. S., Onuchic, J. N., & Wolynes, P. G. (2005). A survey of flexible protein binding mechanisms and their transition states using native topology based energy landscapes. Journal of Molecular Biology, 346(4), 1121–1145. doi:10.1016/j.jmb.2004.12.021
   PubMed Web of Science ®Google Scholar
• Li, Y., Moysey, R., Molloy, P. E., Vuidepot, A.-L., Mahon, T., Baston, E., … Boulter, J. M. (2005). Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nature Biotechnology, 23(3), 349–354. doi:10.1038/nbt1070
   PubMed Web of Science ®Google Scholar
• Ma, B., & Nussinov, R. (2007). Trp/Met/Phe hot spots in protein-protein interactions: Potential targets in drug design. Current Topics in Medicinal Chemistry, 7(10), 999–1005. doi:10.2174/156802607780906717
   PubMed Web of Science ®Google Scholar
• Ma, B., Shatsky, M., Wolfson, H. J., & Nussinov, R. (2009). Multiple diverse ligands binding at a single protein site: A matter of pre-existing populations. Protein Science, 11(2), 184–197. doi:10.1110/ps.21302
   Google Scholar
• Maier, J. A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K. E., & Simmerling, C. (2015). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of Chemical Theory and Computation, 11(8), 3696–3713. doi:10.1021/acs.jctc.5b00255
   PubMed Web of Science ®Google Scholar
• Mason, D. (1998). A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunology Today, 19(9), 395–404. doi:10.1016/S0167-5699(98)01299-7
   PubMedGoogle Scholar
• MATLAB & Statistics Toolbox. (2013). Release The MathWorks Inc., Natick, MA.
   Google Scholar
• Matsui, K., Boniface, J. J., Steffner, P., Reay, P. A., & Davis, M. M. (1994). Kinetics of T-cell receptor binding to peptide/I-Ek complexes: Correlation of the dissociation rate with T-cell responsiveness. Proceedings of the National Academy of Sciences USA, 91(26), 12862–12866. doi:10.1073/pnas.91.26.12862
   PubMed Web of Science ®Google Scholar
• Maverakis, E., van den Elzen, P., & Sercarz, E. E. (2001). Self-reactive T cells and Degeneracy of T Cell Recognition: Evolving concepts-from sequence homology to shape mimicry and TCR flexibility. Journal of Autoimmunity, 16(3), 201–209. doi:10.1006/jaut.2000.0493
   PubMed Web of Science ®Google Scholar
• Mazza, C., Auphan-Anezin, N., Gregoire, C., Guimezanes, A., Kellenberger, C., Roussel, A., … Malissen, B. (2007). How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides? The Embo Journal, 26(7), 1972–1983. doi:10.1038/sj.emboj.7601605
   PubMed Web of Science ®Google Scholar
• Miller, B. R., III, McGee, T. D., Jr, Swails, J. M., Homeyer, N., Gohlke, H., & Roitberg, A. E. (2012). MMPBSA.py: An efficient program for end-state free energy calculations. Journal of Chemical Theory and Computation, 8(9), 3314–3321. doi:10.1021/ct300418h
   PubMed Web of Science ®Google Scholar
• Narzi, D., Becker, C. M., Fiorillo, M. T., Uchanska-Ziegler, B., Ziegler, A., & Böckmann, R. A. (2012). Dynamical characterization of two differentially disease associated MHC class I proteins in complex with viral and self-peptides. Journal of Molecular Biology, 415(2), 429–442. doi:10.1016/j.jmb.2011.11.021
   PubMed Web of Science ®Google Scholar
• Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera-a visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25(13), 1605–1612. doi:10.1002/jcc.20084
   PubMed Web of Science ®Google Scholar
• Reiser, J.-B., Darnault, C., Grégoire, C., Mosser, T., Mazza, G., Kearney, A., … Malissen, B. (2003). CDR3 loop flexibility contributes to the degeneracy of TCR recognition. Nature Immunology, 4(3), 241–247. doi:10.1038/ni891
   PubMed Web of Science ®Google Scholar
• Rognan, D., Zimmermann, N., Jung, G., & Folkers, G. (1992). Molecular dynamics study of a complex between the human histocompatibility antigen HLA-A2 and the IMP58-66 nonapeptide from influenza virus matrix protein. European Journal of Biochemistry, 208(1), 101–113. doi:10.1111/j.1432-1033.1992.tb17163.x
   PubMedGoogle Scholar
• Rueda, M., Ferrer-Costa, C., Meyer, T., Pérez, A., Camps, J., Hospital, A., … Orozco, M. (2007). A consensus view of protein dynamics. Proceedings of the National Academy of Sciences USA, 104(3), 796–801. doi:10.1073/pnas.0605534104
   PubMed Web of Science ®Google Scholar
• Ryckaert, J. P., Ciccotti, G., & Berendsen, H. J. C. (1977). Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics, 23(3), 327–341. doi:10.1016/0021-9991(77)90098-5
   Web of Science ®Google Scholar
• Sami, M., Rizkallah, P. J., Dunn, S., Molloy, P., Moysey, R., Vuidepot, A., … Jakobsen, B. K. (2007). Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry. Protein Engineering, Design and Selection, 20(8), 397–403. doi:10.1093/protein/gzm033
   PubMed Web of Science ®Google Scholar
• Scott, D. R., Borbulevych, O. Y., Piepenbrink, K. H., Corcelli, S. A., & Baker, B. M. (2011). Disparate degrees of hypervariable loop flexibility control T-cell receptor cross-reactivity, specificity, and binding mechanism. Journal of Molecular Biology, 414(3), 385–400. doi:10.1016/j.jmb.2011.10.006
   PubMed Web of Science ®Google Scholar
• Takayuki, A., Ryotaro, K., Akinori, K., & Motonori, O. (2011). PSCDB: A database for protein structural change upon ligand binding. Nucleic Acids Research, 40, D554–D558. doi:10.1093/nar/gkr966
   PubMedGoogle Scholar
• Tsai, C. J., Kumar, S., Ma, B., & Nussinov, R. (1999). Folding funnels, binding funnels, and protein function. Protein Science, 8(6), 1181–1190. doi:10.1110/ps.8.6.1181
   PubMed Web of Science ®Google Scholar
• van der Merwe, P. A., & Davis, S. J. (2003). Molecular interactions mediating T cell antigen recognition. Annual Review of Immunology, 21(1), 659–684. doi:10.1146/annurev.immunol.21.120601.141036
   PubMedGoogle Scholar
• Wan, S., Knapp, B., Wright, D. W., Deane, C. M., & Coveney, P. V. (2015). Rapid, precise, and reproducible prediction of peptide-MHC binding affinities from molecular dynamics that correlate well with experiment. Journal of Chemical Theory and Computation, 11(7), 3346–3356. doi:10.1021/acs.jctc.5b00179
   PubMed Web of Science ®Google Scholar
• Willcox, B. E., Gao, G. F., Wyer, J. R., Ladbury, J. E., Bell, J. I., Jakobsen, B. K., & van der Merwe, P. A. (1999). TCR binding to peptide-MHC stabilizes a flexible recognition interface. Immunity, 10(3), 357–365. doi:10.1016/S1074-7613(00)80035-7
   PubMed Web of Science ®Google Scholar
• Wilson, D. B., Wilson, D. H., Schroder, K., Pinilla, C., Blondelle, S., Houghten, R. A., & Garcia, K. C. (2004). Specificity and degeneracy of T cells. Molecular Immunology, 40(14–15), 1047–1055. doi:10.1016/j.molimm.2003.11.022
   PubMed Web of Science ®Google Scholar
• Wolfson, M. Y., Nam, K., & Chakraborty, A. K. (2011). The effect of mutations on the alloreactive T Cell Receptor/Peptide-MHC interface structure: A molecular dynamics study. The Journal of Physical Chemistry B, 115(25), 8317–8327. doi:10.1021/jp202471d
   PubMed Web of Science ®Google Scholar
• Wu, L. C., Tuot, D. S., Lyons, D. S., Garcia, K. C., & Davis, M. M. (2002). Two-step binding mechanism for T-cell receptor recognition of peptide MHC. Nature, 418(6897), 552–556. doi:10.1038/nature00920
   PubMed Web of Science ®Google Scholar
• Zhan, Y., Carrington, E. M., Zhang, Y., Heinzel, S., & Lew, A. M. (2017). Life and death of activated T Cells: How are they different from Naïve T Cells? Frontiers in Immunology, 8, 1809. doi:10.3389/fimmu.2017.01809
   PubMed Web of Science ®Google Scholar