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Protein folding modulates the chemical reactivity of a Gram-positive adhesin

Nature Chemistry volume 13, pages 172–181 (2021)Cite this article

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Abstract

Gram-positive bacteria colonize mucosal tissues, withstanding large mechanical perturbations such as coughing, which generate shear forces that exceed the ability of non-covalent bonds to remain attached. To overcome these challenges, the pathogen Streptococcus pyogenes utilizes the protein Cpa, a pilus tip-end adhesin equipped with a Cys–Gln thioester bond. The reactivity of this bond towards host surface ligands enables covalent anchoring; however, colonization also requires cell migration and spreading over surfaces. The molecular mechanisms underlying these seemingly incompatible requirements remain unknown. Here we demonstrate a magnetic tweezers force spectroscopy assay that resolves the dynamics of the Cpa thioester bond under force. When folded at forces <6 pN, the Cpa thioester bond reacts reversibly with amine ligands, which are common in inflammation sites; however, mechanical unfolding and exposure to forces >6 pN block thioester reformation. We hypothesize that this folding-coupled reactivity switch (termed a smart covalent bond) could allow the adhesin to undergo binding and unbinding to surface ligands under low force and remain covalently attached under mechanical stress.

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Fig. 1: Mechanochemistry of S. pyogenes Cpa adhesin.
Fig. 2: Dynamics of the thioester-intact Cpa polyprotein under force.
Fig. 3: Cpa thioester bond cleavage is negatively force-dependent.
Fig. 4: Protein folding drives thioester bond reformation.
Fig. 5: Cystamine-mediated abrogation of Cpa thioester bond reformation.
Fig. 6: Bacterium mobility strategy model based on the allosteric modulation of the Cpa thioester bond by protein folding.

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All data supporting the results and conclusions are available within this paper and the Supplementary Information. Source data are provided with this paper.

References

  1. Hall-Stoodley, L., Costerton, J. W. & Stoodley, P. Bacterial biofilms: from the natural environment to infectious diseases. Nat. Rev. Microbiol. 2, 95–108 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Yan, J. & Bassler, B. L. Surviving as a community: antibiotic tolerance and persistence in bacterial biofilms. Cell Host Microbe 26, 15–21 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Forero, M., Yakovenko, O., Sokurenko, E. V., Thomas, W. E. & Vogel, V. Uncoiling mechanics of Escherichia coli type I fimbriae are optimized for catch bonds. PLoS Biol. 4, 1509–1516 (2006).

    Article  CAS  Google Scholar 

  4. Sauer, M. M. et al. Catch-bond mechanism of the bacterial adhesin FimH. Nat. Commun. 7, 10738 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pointon, J. A. et al. A highly unusual thioester bond in a pilus adhesin is required for efficient host cell interaction. J. Biol. Chem. 285, 33858–33866 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Walden, M. et al. An internal thioester in a pathogen surface protein mediates covalent host binding. Elife 4, 1–24 (2015).

    Article  Google Scholar 

  7. Miller, O. K., Banfield, M. J. & Schwarz-Linek, U. A new structural class of bacterial thioester domains reveals a slipknot topology. Protein Sci. 22, 1–50 (2018).

    Google Scholar 

  8. Linke-Winnebeck, C. et al. Structural model for covalent adhesion of the Streptococcus pyogenes pilus through a thioester bond. J. Biol. Chem. 289, 177–189 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Anderson, B. N. et al. Weak rolling adhesion enhances bacterial surface colonization. J. Bacteriol. 189, 1794–1802 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Marshall, K. C. in The Prokaryotes 191–201 (Springer, 2013); https://doi.org/10.1007/978-3-642-30123-0_49

  11. Echelman, D. J., Lee, A. Q. & Fernández, J. M. Mechanical forces regulate the reactivity of a thioester bond in a bacterial adhesin. J. Biol. Chem. 292, 8988–8997 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brouwer, S., Barnett, T. C., Rivera-Hernandez, T., Rohde, M. & Walker, M. J. Streptococcus pyogenes adhesion and colonization. FEBS Lett. 590, 3739–3757 (2016).

    Article  CAS  PubMed  Google Scholar 

  13. Koti Ainavarapu, S. R., Wiita, A. P., Dougan, L., Uggerud, E. & Fernandez, J. M. Single-molecule force spectroscopy measurements of bond elongation during a bimolecular reaction. J. Am. Chem. Soc. 130, 6479–6487 (2008).

    Article  PubMed  CAS  Google Scholar 

  14. Wiita, A. P., Ainavarapu, S. R. K., Huang, H. H. & Fernandez, J. M. Force-dependent chemical kinetics of disulfide bond reduction observed with single-molecule techniques. Proc. Natl Acad. Sci. USA 103, 7222–7227 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wiita, A. P. et al. Probing the chemistry of thioredoxin catalysis with force. Nature 450, 124–127 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schönfelder, J., De Sancho, D. & Perez-Jimenez, R. The power of force: insights into the protein folding process using single-molecule force spectroscopy. J. Mol. Biol. 428, 4245–4257 (2016).

    Article  PubMed  CAS  Google Scholar 

  17. Popa, I. et al. A halotag anchored ruler for week-long studies of protein dynamics. J. Am. Chem. Soc. 138, 10546–10553 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tapia-Rojo, R., Eckels, E. C. & Fernández, J. M. Ephemeral states in protein folding under force captured with a magnetic tweezers design. Proc. Natl Acad. Sci. USA 116, 7873–7878 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Taniguchi, Y. & Kawakami, M. Application of Halotag protein to covalent immobilization of recombinant proteins for single molecule force spectroscopy. Langmuir 26, 10433–10436 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Popa, I. et al. Nanomechanics of halotag tethers. J. Am. Chem. Soc. 135, 12762–12771 (2013).

    Article  CAS  PubMed  Google Scholar 

  21. Zakeri, B. et al. Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Proc. Natl Acad. Sci. USA 109, E690–E697 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Janissen, R. et al. Invincible DNA tethers: covalent DNA anchoring for enhanced temporal and force stability in magnetic tweezers experiments. Nucl. Acids Res. 42, e137 (2014).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Brujić, J., Hermans, R. I. Z., Garcia-Manyes, S., Walther, K. A. & Fernandez, J. M. Dwell-time distribution analysis of polyprotein unfolding using force-clamp spectroscopy. Biophys. J. 92, 2896–2903 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Durner, E., Ott, W., Nash, M. A. & Gaub, H. E. Post-translational sortase-mediated attachment of high-strength force spectroscopy handles. ACS Omega 2, 3064–3069 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Deng, Y. et al. Enzymatic biosynthesis and immobilization of polyprotein verified at the single-molecule level. Nat. Commun. 10, 2775 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Antibiotic Resistance Threats in the United States, 2013 (CDC, 2013).

  27. Cascioferro, S., Cusimano, M. G. & Schillaci, D. Antiadhesion agents against Gram-positive pathogens. Future Microbiol. 9, 1209–1220 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. The Bacterial Challenge: Time to React (ECDC, EMA 2009).

  29. Veggiani, G. et al. Programmable polyproteams built using twin peptide superglues. Proc. Natl Acad. Sci. USA 113, 1202–1207 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Min, D., Arbing, M. A., Jefferson, R. E. & Bowie, J. U. A simple DNA handle attachment method for single molecule mechanical manipulation experiments. Protein Sci. 25, 1535–1544 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Flory, P. J. Theory of elastic mechanisms in fibrous proteins. J. Am. Chem. Soc. 78, 5222–5235 (1956).

    Article  CAS  Google Scholar 

  32. Bell, G. Models for the specific adhesion of cells to cells. Science 200, 618–627 (1978).

    Article  CAS  PubMed  Google Scholar 

  33. Kosuri, P. et al. Protein folding drives disulfide formation. Cell 151, 794–806 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Eckels, E. C., Haldar, S., Tapia-Rojo, R., Rivas-Pardo, J. A. & Fernández, J. M. The mechanical power of titin folding. Cell Rep 27, 1836–1847.e4 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kang, H. J. & Baker, E. N. Intramolecular isopeptide bonds give thermodynamic and proteolytic stability to the major pilin protein of Streptococcus pyogenes. J. Biol. Chem. 284, 20729–20737 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Alegre-Cebollada, J., Badilla, C. L. & Fernández, J. M. Isopeptide bonds block the mechanical extension of pili in pathogenic Streptococcus pyogenes. J. Biol. Chem. 285, 11235–11242 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Echelman, D. J. et al. CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks. Proc. Natl Acad. Sci. USA 113, 2490–2495 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rivas-Pardo, J. A., Badilla, C. L., Tapia-Rojo, R., Alonso-Caballero, Á. & Fernández, J. M. Molecular strategy for blocking isopeptide bond formation in nascent pilin proteins. Proc. Natl Acad. Sci. USA 115, 9222–9227 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang, B., Xiao, S., Edwards, S. A. & Gräter, F. Isopeptide bonds mechanically stabilize Spy0128 in bacterial pili. Biophys. J. 104, 2051–2057 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kang, H. J. & Baker, E. N. Intramolecular isopeptide bonds: protein crosslinks built for stress? Trends Biochem. Sci. 36, 229–237 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Milles, L. F., Schulten, K., Gaub, H. E. & Bernardi, R. C. Molecular mechanism of extreme mechanostability in a pathogen adhesin. Science (80-.) 359, 1527–1533 (2018).

    Article  CAS  Google Scholar 

  42. Herman-Bausier, P. et al. Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion. Proc. Natl Acad. Sci. USA 115, 5564–5569 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Vitry, P. et al. Force-induced strengthening of the interaction between Staphylococcus aureus clumping factor B and loricrin. MBio 8, 1–14 (2017).

    Article  Google Scholar 

  44. Becke, T. D. et al. Pilus-1 backbone protein RrgB of streptococcus pneumoniae binds Collagen I in a force-dependent way. ACS Nano 13, 7155–7165 (2019).

    Article  CAS  PubMed  Google Scholar 

  45. Thomas, W. E., Vogel, V. & Sokurenko, E. Biophysics of catch bonds. Annu. Rev. Biophys. 37, 399–416 (2008).

    Article  CAS  PubMed  Google Scholar 

  46. Sridharan, U. & Ponnuraj, K. Isopeptide bond in collagen- and fibrinogen-binding MSCRAMMs. Biophys. Rev. 8, 75–83 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kreikemeyer, B. et al. Streptococcus pyogenes collagen type I-binding Cpa surface protein: expression profile, binding characteristics, biological functions, and potential clinical impact. J. Biol. Chem. 280, 33228–33239 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Stewart, P. S. Biophysics of biofilm infection. Pathog. Dis. 70, 212–218 (2014).

    Article  CAS  PubMed  Google Scholar 

  49. Law, S. K. & Dodds, A. W. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Sci. 6, 263–274 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Garcia-Ferrer, I. et al. Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition. Proc. Natl Acad. Sci. USA 112, 8290–8295 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wong, S. G. & Dessen, A. Structure of a bacterial α2-macroglobulin reveals mimicry of eukaryotic innate immunity. Nat. Commun. 5, 4917 (2014).

    Article  CAS  PubMed  Google Scholar 

  52. Dodds, A. W., Ren, X.-D., Willis, A. C. & Law, S. K. A. The reaction mechanism of the internal thioester in the human complement component C4. Nature 379, 177–179 (1996).

    Article  CAS  PubMed  Google Scholar 

  53. Nilsson, B. & Nilsson Ekdahl, K. The tick-over theory revisited: is C3 a contact-activated protein? Immunobiology 217, 1106–1110 (2012).

    Article  CAS  PubMed  Google Scholar 

  54. Alegre-Cebollada, J., Perez-Jimenez, R., Kosuri, P. & Fernandez, J. M. Single-molecule force spectroscopy approach to enzyme catalysis. J. Biol. Chem. 285, 18961–18966 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Liang, J. & Fernández, J. M. Mechanochemistry: one bond at a time. ACS Nano 3, 1628–1645 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kahn, T. B., Fernández, J. M. & Perez-Jimenez, R. Monitoring oxidative folding of a single protein catalyzed by the disulfide oxidoreductase DsbA. J. Biol. Chem. 290, 14518–14527 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Carrion-Vazquez, M. et al. The mechanical stability of ubiquitin is linkage dependent. Nat. Struct. Biol. 10, 738–743 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Jagannathan, B., Elms, P. J., Bustamante, C. & Marqusee, S. Direct observation of a force-induced switch in the anisotropic mechanical unfolding pathway of a protein. Proc. Natl Acad. Sci. USA 109, 17820–17825 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dietz, H., Berkemeier, F., Bertz, M. & Rief, M. Anisotropic deformation response of single protein molecules. Proc. Natl Acad. Sci. USA 103, 12724–12728 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Brockwell, D. J. et al. Pulling geometry defines the mechanical resistance of a β-sheet protein. Nat. Struct. Biol. 10, 731–737 (2003).

    Article  CAS  PubMed  Google Scholar 

  61. Stone, K. D., Prussin, C. & Metcalfe, D. D. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol. 125, S73–S80 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Grandbois, M., Beyer, M., Rief, M., Clausen-Schaumann, H. & Gaub, H. E. How strong is a covalent bond. Science 283, 1727–1730 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Pill, M. F., East, A. L. L., Marx, D., Beyer, M. K. & Clausen-Schaumann, H. Mechanical activation drastically accelerates amide bond hydrolysis, matching enzyme activity. Angew. Chem. Int. Ed. 58, 9787–9790 (2019).

    Article  CAS  Google Scholar 

  64. Marshall, BryanT. et al. Direct observation of catch bonds involving cell-adhesion molecules. Nature 423, 190–193 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Tapia-Rojo, R., Alonso-Caballero, A. & Fernandez, J. M. Direct observation of a coil-to-helix contraction triggered by vinculin binding to talin. Sci. Adv. 6, eaaz4707 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Valle-Orero, J. et al. Mechanical deformation accelerates protein ageing. Angew. Chem. Int. Ed. 56, 9741–9746 (2017).

    Article  CAS  Google Scholar 

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Acknowledgements

This research was supported by the National Institutes of Health grant no. R35129962 (J.M.F). A.A-C. and R.T-R. express their gratitude to Fundación Ramón Areces (Madrid, Spain) for financial support. We thank C. L. Badilla for assistance in molecular biology procedures, and for reading and reviewing the manuscript. Correspondence and request for materials should be addressed to A.A-C

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  1. Daniel J. Echelman

    Present address: Boston Combined Residency Program, Boston Children’s Hospital, Boston, MA, USA

  2. Shubhasis Haldar

    Present address: Ashoka University, Haryana, India

  3. These authors contributed equally: Alvaro Alonso-Caballero, Daniel J. Echelman.

Authors and Affiliations

  1. Department of Biological Sciences, Columbia University, New York, NY, USA

    Alvaro Alonso-Caballero, Daniel J. Echelman, Rafael Tapia-Rojo, Shubhasis Haldar, Edward C. Eckels & Julio M. Fernandez

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Contributions

D.J.E., A.A-C. and J.M.F designed the research. A.A-C, D.J.E., R.T-R., S.H., E.C.E carried out the experiments. A.A-C, D.J.E., R.T-R. analysed the data. A.A-C., D.J.E., and J.M.F. wrote the manuscript.

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Correspondence to Alvaro Alonso-Caballero.

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Extended data

Extended Data Fig. 1 Cleavage-reformation-cleavage sequence.

Magnetic tweezers force-clamp trajectory of the Cpa polyprotein. After the unfolding of four thioester-intact Cpa domains at 115 pN (circles, ~ 49 nm), the buffer is exchanged and the polyprotein is exposed to a solution containing 100 mM methylamine (+MA). At 21 pN, four steps appear which account for the release of the polypeptide sequence trapped by the thioester bonds (arrows). Then, the force is increased again to 115 pN, revealing the complete extension of the molecule. Immediately after, MA is washed out from the fluid chamber and the polyprotein is allowed to fold and reform the thioester bonds for 100 s at 4.5 pN. A 115 pN pulse reveals three ~ 95 nm steps (empty circles) which correspond with the full extension of Cpa, and one Cpa domain with its thioester bond reformed (circles, ~ 49 nm). Two more quenches at 3 pN are applied to completely recover the thioester-reformed state in all the four domains, as it can be seen in the 115 pN pulse applied approximately after 800 s of experiment (circles). Then, MA is added again and the force quenched to 24 pN to trigger again the cleavage of the thioester bonds of the polyprotein (arrows).

Extended Data Fig. 2 Cystamine permanent blocking of Cpa thioester bond reformation.

Magnetic tweezers force-clamp trajectory of the Cpa polyprotein. After the unfolding of the thioester-intact Cpa domains at 115 pN (circles), the buffer is exchanged and the polyprotein is exposed to a solution containing 100 mM cystamine (+CA). At 115 pN and at 50 pN, no additional extensions are registered as a consequence of thioester bond cleavage, but a drop in force to 25 pN leads to the appearance of four steps which account for the release of the polypeptide sequence trapped by the thioester bonds (empty arrows in the inset). Then, the force is increased again to 115 pN, revealing the complete extension of the molecule. After 100 s at 4 pN and in the presence of CA, a 115 pN pulse reveals three ~95 nm steps (empty circles) which correspond with the full extension of Cpa. CA is then removed from the solution, and several consecutive 100 s force quenches (at 4, 5, and 3 pN) followed by 115 pN pulses are applied. These cycles reveal that, after CA treatment, Cpa is able to fold but not to reform its thioester bond, as it can be observed from the ~95 nm steps observed (empty circles). After the first 300 s of the experiment, one of the Cpa domains stops folding back as a consequence of oxidative damage66. The disturbances observed in the extension during +CA addition (orange block) and washing (gray block) are originated from the movement of buffer volumes in the liquid cell used in the experiments, which transiently alter the measurement.

Extended Data Fig. 3 TCEP rescues Cpa thioester bond reformation.

A Cpa polyprotein previously treated with cystamine shows three ~95 nm steps at 115 pN corresponding with the full extension of each of the domains (empty circles). The addition of 10 mM TCEP and 100 s at 4 pN is enough to trigger thioester bond reformation, as it can be observed in the ~49 nm thioester-intact Cpa steps (circles) registered at 115 pN. The fourth domain not observed at the beginning was probably unfolded and its thioester bond intact, since the difference in the final extension between the first 115 pN pulse and the last is ~140 nm, which matches with the expected final extension decrease from three reformation events. Inset histogram shows the two populations of steps observed after TCEP treatment, thioester-intact Cpa (circles, 48.3 ± 3.5 nm, mean±SD, n=32) and thioester-cleaved Cpa (empty circles, 95.7 ± 6.4 nm mean±SD, n=7). The latter full length steps of Cpa after TCEP treatment could be due to cleavage events induced by remaining cystamine which was not completely washed from the experimental liquid cell. The disturbances observed in the extension during +TCEP addition (green block) are originated from the movement of buffer volumes in the liquid cell used in the experiments, which transiently alter the measurement.

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Alonso-Caballero, A., Echelman, D.J., Tapia-Rojo, R. et al. Protein folding modulates the chemical reactivity of a Gram-positive adhesin. Nat. Chem. 13, 172–181 (2021). https://doi.org/10.1038/s41557-020-00586-x

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