Log in

Human and Tree Shrew Alpha-synuclein: Comparative cDNA Sequence and Protein Structure Analysis

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The synaptic protein alpha-synuclein (α-syn) is associated with a number of neurodegenerative diseases, and homology analyses among many species have been reported. Nevertheless, little is known about the cDNA sequence and protein structure of α-syn in tree shrews, and this information might contribute to our understanding of its role in both health and disease. We designed primers to the human α-syn cDNA sequence; then, tree shrew α-syn cDNA was obtained by RT-PCR and sequenced. Based on the acquired tree shrew α-syn cDNA sequence, both the amino acid sequence and the spatial structure of α-syn were predicted and analyzed. The homology analysis results showed that the tree shrew cDNA sequence matches the human cDNA sequence exactly except at nucleotide positions 45, 60, 65, 69, 93, 114, 147, 150, 157, 204, 252, 270, 284, 298, 308, and 324. Further protein sequence analysis revealed that the tree shrew α-syn protein sequence is 97.1 % identical to that of human α-syn. The secondary protein structure of tree shrew α-syn based on random coils and α-helices is the same as that of the human structure. The phosphorylation sites are highly conserved, except the site at position 103 of tree shrewα-syn. The predicted spatial structure of tree shrew α-syn is identical to that of human α-syn. Thus, α-syn might have a similar function in tree shrew and in human, and tree shrew might be a potential animal model for studying the pathogenesis of α-synucleinopathies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Arnold, K., Bordoli, L., Kopp, J., & Schwede, T. (2006). The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics, 22, 195–201.

    Article  CAS  Google Scholar 

  2. Auluck, P. K., Caraveo, G., & Lindquist, S. (2010). Alpha-synuclein: membrane interactions and toxicity in Parkinson’s disease. Annual Review of Cell and Developmental Biology, 26, 211–233.

    Article  CAS  Google Scholar 

  3. Bartolomucci, A., de Biurrun, G., & Fuchs, E. (2001). How tree shrews (Tupaia belangeri) perform in a searching task: evidence for strategy use. Journal of Comparative Psychology, 115, 344–350.

    Article  CAS  Google Scholar 

  4. Blom, N., Gammeltoft, S., & Brunak, S. (1999). Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. Journal of Molecular Biology, 294, 1351–1362.

    Article  CAS  Google Scholar 

  5. Bussell Jr., R., & Eliezer, D. (2001). Residual structure and dynamics in Parkinson’s disease-associated mutants of alpha-synuclein. The Journal of Biological Chemistry, 276, 45996–46003.

    Article  CAS  Google Scholar 

  6. Cao, J., Yang, E. B., Su, J. J., Li, Y., & Chow, P. (2003). The tree shrews: adjuncts and alternatives to primates as models for biomedical research. Journal of Medical Primatology, 32, 123–130.

    Article  CAS  Google Scholar 

  7. Conway, K. A., Harper, J. D., & Lansbury Jr., P. T. (2000). Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson’s disease are typical amyloid. Biochemistry, 39, 2552–2563.

    Article  CAS  Google Scholar 

  8. Cooper, A. A., Gitler, A. D., Cashikar, A., Haynes, C. M., Hill, K. J., Bhullar, B., Liu, K., Xu, K., Strathearn, K. E., Liu, F., Cao, S., Caldwell, K. A., Caldwell, G. A., Marsischky, G., Kolodner, R. D., Labaer, J., Rochet, J. C., Bonini, N. M., & Lindquist, S. (2006). Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson’s models. Science, 313, 324–328.

    Article  CAS  Google Scholar 

  9. Czeh, B., Michaelis, T., Watanabe, T., Frahm, J., de Biurrun, G., van Kampen, M., Bartolomucci, A., & Fuchs, E. (2001). Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proceedings of the National Academy of Sciences of the United States of America, 98, 12796–12801.

    Article  CAS  Google Scholar 

  10. Davidson, W. S., Jonas, A., Clayton, D. F., & George, J. M. (1998). Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. The Journal of Biological Chemistry, 273, 9443–9449.

    Article  CAS  Google Scholar 

  11. Dickson, D. W., Crystal, H. A., Mattiace, L. A., Masur, D. M., Blau, A. D., Davies, P., Yen, S. H., & Aronson, M. K. (1992). Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiology of Aging, 13, 179–189.

    Article  CAS  Google Scholar 

  12. Fuchs, E. (2005). Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder. CNS Spectrums, 10, 182–190.

    Google Scholar 

  13. Fuchs, E., & Flugge, G. (2002). Social stress in tree shrews: effects on physiology, brain function, and behavior of subordinate individuals. Pharmacology, Biochemistry, and Behavior, 73, 247–258.

    Article  CAS  Google Scholar 

  14. Fuchs, E., Uno, H., & Flugge, G. (1995). Chronic psychosocial stress induces morphological alterations in hippocampal pyramidal neurons of the tree shrew. Brain Research, 673, 275–282.

    Article  CAS  Google Scholar 

  15. Giasson, B. I., Murray, I. V., Trojanowski, J. Q., & Lee, V. M. (2001). A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. The Journal of Biological Chemistry, 276, 2380–2386.

    Article  CAS  Google Scholar 

  16. Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A., & Fuchs, E. (1997). Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. The Journal of Neuroscience, 17, 2492–2498.

    CAS  Google Scholar 

  17. Guex, N., & Peitsch, M. C. (1997). SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis, 18, 2714–2723.

    Article  CAS  Google Scholar 

  18. Hong, L., Ko, H. W., Gwag, B. J., Joe, E., Lee, S., Kim, Y. T., & Suh, Y. H. (1998). The cDNA cloning and ontogeny of mouse alpha-synuclein. Neuroreport, 9, 1239–1243.

    Article  CAS  Google Scholar 

  19. Jakes, R., Spillantini, M. G., & Goedert, M. (1994). Identification of two distinct synucleins from human brain. FEBS Letters, 345, 27–32.

    Article  CAS  Google Scholar 

  20. Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998). Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nature Genetics, 18, 106–108.

    Article  CAS  Google Scholar 

  21. Lavedan, C. (1998). The synuclein family. Genome Research, 8, 871–880.

    CAS  Google Scholar 

  22. Lee, S. B., Park, S. M., Ahn, K. J., Chung, K. C., Paik, S. R., & Kim, J. (2009). Identification of the amino acid sequence motif of alpha-synuclein responsible for macrophage activation. Biochemical and Biophysical Research Communications, 381, 39–43.

    Article  CAS  Google Scholar 

  23. Li, J., Uversky, V. N., & Fink, A. L. (2001). Effect of familial Parkinson’s disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein. Biochemistry, 40, 11604–11613.

    Article  CAS  Google Scholar 

  24. Maroteaux, L., Campanelli, J. T., & Scheller, R. H. (1988). Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. The Journal of Neuroscience, 8, 2804–2815.

    CAS  Google Scholar 

  25. McCoy, P., Norton, T. T., & McMahon, L. L. (2008). Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation. Journal of Neurophysiology, 100, 336–345.

    Article  CAS  Google Scholar 

  26. Mori, F., Nishie, M., Kakita, A., Yoshimoto, M., Takahashi, H., & Wakabayashi, K. (2006). Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. Journal of Neuropathology and Experimental Neurology, 65, 808–815.

    Article  CAS  Google Scholar 

  27. Norris, E. H., Giasson, B. I., & Lee, V. M. (2004). Alpha-synuclein: normal function and role in neurodegenerative diseases. Current Topics in Developmental Biology, 60, 17–54.

    Article  CAS  Google Scholar 

  28. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G., Lazzarini, A. M., Duvoisin, R. C., Di Iorio, G., Golbe, L. I., & Nussbaum, R. L. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science, 276, 2045–2047.

    Article  CAS  Google Scholar 

  29. Rospigliosi, C. C., McClendon, S., Schmid, A. W., Ramlall, T. F., Barre, P., Lashuel, H. A., & Eliezer, D. (2009). E46K Parkinson’s-linked mutation enhances C-terminal-to-N-terminal contacts in alpha-synuclein. Journal of Molecular Biology, 388, 1022–1032.

    Article  CAS  Google Scholar 

  30. Schwede, T., Kopp, J., Guex, N., & Peitsch, M. C. (2003). SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Research, 31, 3381–3385.

    Article  CAS  Google Scholar 

  31. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature, 388, 839–840.

    Article  CAS  Google Scholar 

  32. Surguchov, A., McMahan, B., Masliah, E., & Surgucheva, I. (2001). Synucleins in ocular tissues. Journal of Neuroscience Research, 65, 68–77.

    Article  CAS  Google Scholar 

  33. Touchman, J. W., Dehejia, A., Chiba-Falek, O., Cabin, D. E., Schwartz, J. R., Orrison, B. M., Polymeropoulos, M. H., & Nussbaum, R. L. (2001). Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element. Genome Research, 11, 78–86.

    Article  CAS  Google Scholar 

  34. Ueda, K., Fukushima, H., Masliah, E., **a, Y., Iwai, A., Yoshimoto, M., Otero, D. A., Kondo, J., Ihara, Y., & Saitoh, T. (1993). Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 90, 11282–11286.

    Article  CAS  Google Scholar 

  35. Vekrellis, K., Rideout, H. J., & Stefanis, L. (2004). Neurobiology of alpha-synuclein. Molecular Neurobiology, 30, 1–21.

    Article  CAS  Google Scholar 

  36. Wang, J., Zhou, Q., Tian, M., Yang, Y., & Xu, L. (2011). Tree shrew models: a chronic social defeat model of depression and a one-trial captive conditioning model of learning and memory. Zool Res, 32, 24–30.

    Google Scholar 

  37. Xu, L., Fan, Y., Jiang, X., & Yao, Y. (2013). Molecular evidence on the phylogenetic position of tree shrew (Tupia belangeri). Zool Res, 34, 70–76.

    Article  CAS  Google Scholar 

  38. Yamashita, A., Fuchs, E., Taira, M., & Hayashi, M. (2010). Amyloid beta (Abeta) protein- and amyloid precursor protein (APP)-immunoreactive structures in the brains of aged tree shrews. Current Aging Science, 3, 230–238.

    Article  CAS  Google Scholar 

  39. Zarranz, J. J., Alegre, J., Gomez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atares, B., Llorens, V., Gomez Tortosa, E., del Ser, T., Munoz, D. G., & de Yebenes, J. G. (2004). The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Annals of Neurology, 55, 164–173.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China Grants (No. 81274122, 81301073, U1402221), the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20121106120056, 20121106130001), Yunnan Natural Science Foundation (No. 2011FB116, 2013FZ132, 2014FB191), the PUMC Youth Fund and the Fundamental Research Funds for the Central Universities (No. 3332013082, 3332013146, 33320140191), Bei**g Natural Science Foundation (No. 7131013), the Fund for the Institute of Medical Biology (No. IMB2013YB01, 2014IMB01ZD), and the Fund for the Institute of Pathogen Biology, Chinese Academy of Medical Sciences (No. 2015IPB201).

Conflict of Interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kai-Li Ma.

Additional information

Zheng-Cun Wu and Zhang-Qiong Huang these authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, Z.C., Huang, ZQ., Jiang, QF. et al. Human and Tree Shrew Alpha-synuclein: Comparative cDNA Sequence and Protein Structure Analysis. Appl Biochem Biotechnol 177, 957–966 (2015). https://doi.org/10.1007/s12010-015-1789-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-015-1789-6

Keywords

Navigation