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Computational Studies of the Interaction of Chitosan Nanoparticles and αB-Crystallin

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Abstract

αB-Crystallin is a small heat shock protein associated with numerous degenerative diseases and abnormal growth patterns. The development of protein–nanoparticle conjugates is a motivation to investigate αB-crystallin domain (ACD) as a part of treatment regime. Molecular docking simulations were applied to localize the potential interaction sites of chitosan (CS). These studies revealed that chitosan forms H-bonds with K92A, E99A, E117A, and E117B amino acid residues of ACD. Molecular dynamics simulations with explicit water molecules of both the native ACD of the protein and a ligand–protein complex showed that the potential energy of ACD-CS complex is lesser than the native ACD. The structure of the ACD-CS complex showed low root mean square deviation (RMSD) with respect to its reference positioning. The flexibility of ACD-CS complex as indicated by a root-mean-square fluctuation analysis indicated similarities overall, with some residue specific differences for G27, E42, T64, and P80 that are situated prior to a flexible loops. The flexibility of these residues was notably larger in the protein–ligand complex form. In addition, the number of hydrogen bonds is constant throughout the 2-ns simulation. Analyses of MD trajectories for native ACD and ACD-CS complex revealed subtle structure variation between the subunits of the dimer. However, the secondary structures of both models remain close to their starting structures. The potential utilization of αB-crystallin domain/chitosan complex as a therapeutic agent for crystallinopathy is paramount.

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References

  1. Jain, K. K. (2008). Nanomedicine: application of nanobiotechnology in medical practice. Medical Principles and Practice, 17, 89–101.

    Article  Google Scholar 

  2. George, D. F., Bilek, M. M. M., McKenzie, D. R. (2008). Detecting and exploring partially folded states of proteins using a sensor with chaperone bound to its surface. Biosensors and Bioelectronics, 24, 963–969.

    Article  Google Scholar 

  3. Rasmussen, T., Tantipolphan, R., van de Weert, M., Jiskoot, W. (2010). The molecular chaperone a-crystallin as an excipient in an insulin formulation. Pharmaceutical Research, 27, 1337–1347.

    Article  Google Scholar 

  4. Horwitz, J. (2009). Alpha crystallin: The quest for a homogeneous quaternary structure. Experimental Eye Research, 88, 190–194.

    Article  Google Scholar 

  5. de Jong, W. W., Lubsen, N. H., Kraft, H. J. (1994). Molecular evolution of the eye lens. Progress Retinal Eye Research, 13, 391–442.

    Article  Google Scholar 

  6. Siezen, R. J., Bindels, J. G., Hoenders, H. J. (1978). The quaternary structure of bovine alpha-crystallin. Size and charge microheterogeneity: more than 1000 different hybrids? European Journal of Biochemistry, 91, 387–396.

    Article  Google Scholar 

  7. Haley, D. A., Horwitz, J., Stewart, P. L. (1998). The small heat-shock protein, alphaB-crystallin, has a variable quaternary structure. Journal of Molecular Biology, 277, 27–35.

    Article  Google Scholar 

  8. Horwitz, J. (2003). Alpha-crystallin. Experimental Eye Research, 76, 145–153.

    Article  Google Scholar 

  9. Bhat, S. P., & Nagineni, C. N. (1989). αB subunit of lens-specific protein alpha-crystallin is present in other ocular and non-ocular tissues. Biochemical and Biophysical Research Communications, 158, 319–325.

    Article  Google Scholar 

  10. Dubin, R. A., Wawrousek, E. F., Piatigorsky, J. (1989). Expression of the murine aB-crystallin is not restricted to the lens. Molecular and Cellular Biology, 9, 1083–1091.

    Google Scholar 

  11. Perng, M. D., Wen, S. F., van den Ijssel, P., Prescott, A. R., Quinlan, R. A. (2004). Desmin aggregate formation by R120G alphaB-crystallin is caused by altered filament interactions and is dependent upon network status in cells. Molecular Biology of the Cell, 15, 2335–2346.

    Article  Google Scholar 

  12. Magalhães, J., Santos, S. D., Saraiva, M. J. (2010). αB-crystallin (HspB5) in familial amyloidotic polyneuropathy. International Journal of Experimental Pathology, 91, 515–521.

    Article  Google Scholar 

  13. Fort, P. E., & Lampi, K. J. (2011). New focus on alpha-crystallins in retinal neurodegenerative diseases. Experimental Eye Research, 92, 98–103.

    Article  Google Scholar 

  14. Sanbe, A. (2011). Molecular mechanisms of α-crystallinopathy and its therapeutic strategy. Biological and Pharmaceutical Bulletin, 34, 1653–1658.

    Article  Google Scholar 

  15. Kato, K., Shinohara, H., Kurobe, N., Goto, S., Inaguma, Y., Ohshima, K. (1991). Immunoreactive alpha A crystallin in rat nonlenticular tissues detected with a sensitive immunoassay method. Biochimica et Biophysica Acta, 1080, 173–180.

    Article  Google Scholar 

  16. de Jong, W. W., Caspers, G. J., Leunissen, J. A. (1998). Geneology of the alpha-crystallin-small heat-shock protein superfamily. International Journal of Biological Macromolecules, 22, 151–162.

    Article  Google Scholar 

  17. Sun, T. X., Akhtar, N. J., Liang, J. J. (1999). Thermodynamic stability of human recombinant αA- and αB-crystallins. Journal of Biological Chemistry, 274, 34067–34071.

    Article  Google Scholar 

  18. Abgar, S., Beckmann, J., Aerts, T., Vanhoudt, J., Clauwaert, J. (2000). The structural differences between bovine lens αA- and αB-crystallin. European Journal of Biochemistry, 267, 5916–5925.

    Google Scholar 

  19. Liang, J. J., Sun, T. X., Akhtar, N. J. (2000). Heat-induced conformational changes of human recombinant αA- and αB-crystallins. Molecular Vision, 6, 10–14.

    Google Scholar 

  20. Andley, U. P., Song, Z., Wawrousek, E. F., Fleming, T. P., Bassnett, S. (2000). Differential protective activity of αA- and αB-crystallin in lens epithelial cells. Journal of Biological Chemistry, 275, 36823–36831.

    Article  Google Scholar 

  21. Takeuchi, S., Mandai, Y., Otsu, A., Shirakawa, T., Masuda, K., Chinami, M. (2003). Differences in properties between human alphaA- and alphaB-crystallin proteins expressed in Escherichia coli cells in response to cold and extreme pH. Biochemical Journal, 375, 471–475.

    Article  Google Scholar 

  22. Fisher, M. T. (2006). Proline to the rescue. Proceedings of the National Academy of Science USA, 103, 13265–13266.

    Article  Google Scholar 

  23. Hatters, D. M., Lindner, R. A., Carver, J. A., Howlett, G. J. (2001). The molecular chaperone, alpha-crystallin, inhibits amyloid formation by apolipoprotein C-II. Journal of Biological Chemistry, 276, 33755–33761.

    Article  Google Scholar 

  24. Kudva, Y. C., Hiddinga, H. J., Butler, P. C., Mueske, C. S., Eberhardt, N. L. (1997). Small heat shock proteins inhibit in vitro A beta(1–42) amyloidogenesis. FEBS Letters, 416, 117–121.

    Article  Google Scholar 

  25. Stege, G. J., Renkawek, K., Overkamp, P. S., Verschuure, P., van Rijk, A. F., Reijnen-Aalbers, A., et al. (1999). The molecular chaperone alphaB-crystallin enhances amyloid beta neurotoxicity. Biochemical and Biophysical Research Communications, 262, 152–156.

    Article  Google Scholar 

  26. Rekas, A., Jankova, L., Carver, J. A. (2007). Monitoring the prevention of amyloid fibril formation by α-crystallin. Temperature dependence and the nature of the aggregating species. FEBS Journal, 274, 6290–6304.

    Article  Google Scholar 

  27. Waudby, C. A., Knowles, T. P., Devlin, G. L., Skepper, J. N., Ecroyd, H., Carver, J. A., et al. (2010). The interaction of alphaB-crystallin with mature alpha-synuclein amyloid fibrils inhibits their elongation. Biophysical Journal, 98, 843–851.

    Article  Google Scholar 

  28. Tiyaboonchai, W. (2003). Chitosan nanoparticles: a promising system for drug delivery. Naresuan University Journal, 11, 51.

    Google Scholar 

  29. Yi, H., Wu, L. Q., Bentley, W. E., Ghodssi, R., Rubloff, G. W., Culver, J. N., et al. (2005). Biofabrication with Chitosan. Biomacromolecules, 6, 2881–2894.

    Article  Google Scholar 

  30. Jayakumar, R., New, N., Tokura, S., Tamura, H. (2007). Sulfated chitin and chitosan as novel biomaterials. International Journal of Biological Macromolecules, 40, 175–181.

    Article  Google Scholar 

  31. Mourya, V. K., & Inamdar, N. N. (2008). Chitosan-modifications and applications: opportunities galore. Reactive and Functional Polymers, 68, 1013–1051.

    Article  Google Scholar 

  32. Ibrahim, M., & Gawad, A. E. (2012). Spectroscopic analyses of chitosan interactions with amino acids. Journal of Computational and Theoretical Nanoscience, 9, 1120–1124.

    Article  Google Scholar 

  33. Ibrahim, M., Osman, O., Mahmoud, A. A. (2011). Spectroscopic analyses of cellulose and chitosan: FTIR and modeling approach. Journal of Computational and Theoretical Nanoscience, 8, 117–1123.

    Article  Google Scholar 

  34. Ibrahim, M., Osman, O., Refaat, A., El-Sayed, M. E. (2010). Molecular spectroscopic analyses of nano chitosan blend as biosensor. Spectrochimica Acta Part A, 77, 802–806.

    Article  Google Scholar 

  35. El-Sayed, M. E., Omar, A., Ibrahim, M., Abdel-Fattah, W. I. (2009). On the structural analysis and electronic properties of chitosan/hydroxyapatite interaction. Journal of Computational and Theoretical Nanoscience, 6, 1663–1669.

    Article  Google Scholar 

  36. Jehle, S., Rajagopal, P., Bardiaux, B., Markovic, S., Kühne, R., Stout, J. R., et al. (2010). Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers. Nature Structural and Molecular Biology, 17, 1037–1042.

    Article  Google Scholar 

  37. Rodriguez, R., Chinea, G., Lopez, N., Pons, T., Vriend, G. (1998). Homology modeling, model and software evaluation: three related resources. Bioinformatics, 14, 523–528.

    Article  Google Scholar 

  38. Schüttelkopf, A. W., & van Aalten, D. M. (2004). PRODRG - a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallographica, D60, 1355–1363.

    Google Scholar 

  39. Lindorff-Larsen, K., Piana, S., Palmo, K., Maragakis, P., Klepeis, J. L., Dror, R. O., et al. (2010). Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins, 78, 1950–1958.

    Google Scholar 

  40. Kirschner, K. N., Yongye, A. B., Tschampel, S. M., González-Outeiriño, J., Daniels, C. R., Foley, B. L., et al. (2008). GLYCAM06: A generalized biomolecular force field. Carbohydrates Journal of Computational Chemistry, 29, 622–655.

    Article  Google Scholar 

  41. Case, D. A., Cheatham, T. E., 3rd, Darden, T., Gohlke, H., Luo, R., Merz, K. M., Jr., et al. (2005). The Amber biomolecular simulation programs. Journal of Computational Chemistry, 26, 1668–1688.

    Article  Google Scholar 

  42. Ryckaert, J. P., Ciccotti, G., Berendsen, 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, 327–341.

    Article  Google Scholar 

  43. Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. Journal of Chemical Physics, 81, 3684–3690.

    Article  Google Scholar 

  44. Humphrey, W., Dalke, A., Schulten, K. (1996). VMD: visual molecular dynamics. Journal of Molecular Graphics, 14, 33–38.

    Article  Google Scholar 

  45. Grabowski, S. J. (2004). Hydrogen bonding strength—measures based on geometric and topological parameters. Journal of Physical Organic Chemistry, 17, 18–31.

    Article  Google Scholar 

  46. Andley, U. P. (2007). Crystallins in the eye: Function and pathology. Progress in Retinal and Eye Research, 26, 78–98.

    Article  Google Scholar 

  47. Selcen, D. (2011). Myofibrillar myopathies. Neuromuscular Disorders, 21, 161–171.

    Article  Google Scholar 

  48. Graw, J. (2009). Genetics of crystallins: cataract and beyond. Experimental Eye Research, 88, 173–189.

    Article  Google Scholar 

  49. Ecroyd, H., & Carver, J. A. (2009). Crystallin proteins and amyloid fibrils. Cellular and Molecular Life Sciences, 66, 62–81.

    Article  Google Scholar 

  50. Singha, S., Bhattacharya, J., Datta, H., Dasgupta, A. K. (2009). Anti-glycation activity of gold nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine, 5, 21–29.

    Article  Google Scholar 

  51. Wang, X., Chi, N., Tang, X. (2008). Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. European Journal of Pharmaceutics and Biopharmaceutics, 70, 735–740.

    Article  Google Scholar 

  52. Cabaleiro-Lago, C., Szczepankiewicz, O., Linse, S. (2013). The effect of nanoparticles on amyloid aggregation depends on the protein stability and intrinsic aggregation rate. Langmuir, 28, 1852–1857.

    Article  Google Scholar 

  53. Asomugha, C. O., & Srivastiva, O. P. (2011). Structural and functional properties of NH2-terminal domain, core domain, and COOH-terminal extension of αA- and αB-crystallins. Molecular Vision, 17, 2356–2367.

    Google Scholar 

  54. Ghosh, J. G., & Clark, J. I. (2006). Insight into the domains required for dimerization and assembly of human αB-crystallin.

  55. Bloemendal, H., de Jong, W. W., Jaenicke, R., Lubsen, N. H., Slingsby, C., Tardieu, A. (2004). Ageing and vision: structure, stability and function of lens crystallins. Progress in Biophysics and Molecular Biology, 86, 407–485.

    Article  Google Scholar 

  56. Bagnéris, C., Bateman, O. A., Naylor, C. E., Cronin, N., Boelens, W. C., Keep, N. H., et al. (2009). Crystal structures of alpha-crystallin domain dimers of alphaB-crystallin and Hsp20. Journal of Molecular Biology, 392, 1242–1252.

    Article  Google Scholar 

  57. Laganowsky, A., Benesch, J. L., Landau, M., Ding, L., Sawaya, M. R., Cascio, D., et al. (2010). Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens function. Protein Science, 19, 1031–1043.

    Article  Google Scholar 

  58. Baldwin, A. J., Lioe, H., Hilton, G. R., Baker, L. A., Rubinstein, J. L., Kay, L. E., et al. (2011). The polydispersity of αB-crystallin is rationalized by an interconverting polyhedral architecture. Structure, 19, 1855–1863.

    Article  Google Scholar 

  59. Kim, K. K., Kim, R., Kim, S. H. (1998). Crystal structure of a small heat-shock protein. Nature, 394, 595–599.

    Article  Google Scholar 

  60. Van Montfort, R., Slingsby, C., Vierlingt, E. (2001). Structure and function of the small heat shock protein/α-crystallin family of molecular chaperones. Advances in Protein Chemistry, 59, 105–156.

    Article  Google Scholar 

  61. Abraham, E. C., Cherian, M., Smith, J. B. (1994). Site selectivity in the glycation of alpha A- and alpha B-crystallins by glucose. Biochemical and Biophysical Research Communications, 201, 1451–1456.

    Article  Google Scholar 

  62. Kumar, P. A., Kumar, M. S., Reddy, G. B. (2007). Effect of glycation on α-crystallin structure and chaperone-like function. Biochemistry Journal, 408, 251–258.

    Article  Google Scholar 

  63. Fei, L., & Perrett, S. (2009). Effect of nanoparticles on protein folding and fibrillogenesis. International Journal of Molecular Sciences, 10, 646–656.

    Article  Google Scholar 

  64. Vertegel, A. A., Siegel, R. W., Dordick, J. S. (2004). Silica nanoparticle size influences the structure and enzymatic activity of adsorbed lysozyme. Langmuir, 20, 6800–6807.

    Article  Google Scholar 

  65. Shang, W., Nuffer, J. H., Dordick, J. S., Siegel, R. W. (2007). Unfolding of ribonuclease A on silica nanoparticle surfaces. Nano Letters, 7, 1991–1995.

    Article  Google Scholar 

  66. Xue, W. F., Hellewell, A. L., Gosal, W. S., Homans, S. W., Hewitt, E. W., Radford, S. E. (2009). Fibril fragmentation enhances amyloid cytotoxicity. Journal of Biological Chemistry, 284, 34272–34282.

    Article  Google Scholar 

  67. Sánchez, L., Madurga, S., Pukala, T., Vilaseca, M., López-Iglesias, C., Robinson, C. V., et al. (2011). Aβ40 and Aβ42 amyloid fibrils exhibit distinct molecular recycling properties. Journal of the American Chemical Society, 133, 6505–6508.

    Article  Google Scholar 

  68. Shammas, S. L., Waudby, C. A., Wang, S., Buell, A. K., Knowles, T. P., Ecroyd, H., et al. (2011). Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation. Biophysical Journal, 101, 1681–1689.

    Article  Google Scholar 

  69. Ghosh, J. G., Houck, S. A., Clark, J. I. (2008). Interactive sequences in the molecular chaperone, human alphaB crystallin modulate the fibrillation of amyloidogenic proteins. The International Journal of Biochemistry & Cell Biology, 40, 954–967.

    Article  Google Scholar 

  70. Feil, I. K., Malfois, M., Hendle, J., van Der Zandt, H., Svergun, D. I. (2001). A novel quaternary structure of the dimeric alpha-crystallin domain with chaperone-like activity. Journal of Biological Chemistry, 276, 12024–12029.

    Article  Google Scholar 

  71. Ghosh, J. G., Estrada, M. R., Houck, S. A., Clark, J. I. (2005). The function of the β3 interactive domain in the small heat shock protein and molecular chaperone, human αB crystalline. Cell Stress & Chaperones, 11, 187–197.

    Article  Google Scholar 

  72. Bhattacharyya, J., Udupa, E. G. P., Wang, J., Sharma, K. K. (2006). Mini-αB-crystallin: A functional element of αB-crystallin with chaperone-like activity. Biochemistry, 45, 3069–3076.

    Article  Google Scholar 

  73. Ghosh, J. G., Houck, S. A., Doneanu, C. E., Clark, J. I. (2006). The beta4-beta8 groove is an ATP-interactive site in the alpha crystallin core domain of the small heat shock protein, human alphaB crystalline. Journal of Molecular Biology, 364, 364–375.

    Article  Google Scholar 

  74. Arac, A., Brownell, S. E., Rothbard, J. B., Chen, C., Ko, R. M., Pereira, M. P., et al. (2011). Systemic augmentation of alphaB-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation. Proceedings of the National Academy of Sciences USA, 108, 13287–13292.

    Article  Google Scholar 

  75. Ousman, S. S., Tomooka, B. H., van Noort, J. M., Wawrousek, E. F., O’Connor, K. C., Hafler, D. A., et al. (2007). Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Nature, 448, 474–479.

    Article  Google Scholar 

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Acknowledgments

I thank Professor Case DA for providing me the Amber8 package.

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  1. Biophysics and Laser Science Unit, Research Institute of Ophthalmology, 2, Al-Ahram St, Giza, 12111, Egypt

    Alaa El-Din A. Gawad

  2. Spectroscopy Department, National Research Center, Dokki, Cairo, Egypt

    Medhat Ibrahim

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Correspondence to Alaa El-Din A. Gawad.

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Gawad, A.ED.A., Ibrahim, M. Computational Studies of the Interaction of Chitosan Nanoparticles and αB-Crystallin. BioNanoSci. 3, 302–311 (2013). https://doi.org/10.1007/s12668-013-0096-3

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