Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 350-357 , December 2008

Mechanism of alpha-synuclein oligomerization and membrane interaction: theoretical approach to unstructured proteins studies

  • Igor F. Tsigelny, PhD

      Affiliations

    • Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California
    • San Diego Supercomputer Center, University of California San Diego, La Jolla, California
    • Corresponding Author InformationCorresponding author. University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0444, USA.
    • ,
  • Yuriy Sharikov

      Affiliations

    • San Diego Supercomputer Center, University of California San Diego, La Jolla, California
    • ,
  • Mark A. Miller, PhD

      Affiliations

    • San Diego Supercomputer Center, University of California San Diego, La Jolla, California
    • ,
  • Eliezer Masliah, MD

      Affiliations

    • Departments of Neurosciences and Pathology, University of California San Diego, La Jolla, California, USA

Received 4 January 2008 ,Accepted 5 May 2008.

References 

  1. Kransnoslobodtsev AV, Shlyakhtenko LS, Ukraintsev E, Zaikova TO, Keana JF, Lyubchenko YL. Nanomedicine and protein misfolding diseases. Nanomedicine. 2005;1:300–305
  2. Jellinger KA. Neuropathological aspects of Alzheimer disease, Parkinson disease and frontotemporal dementia. Neurodegener Dis. 2008;5:118–121
  3. Shewmaker F, Ross ED, Tycko R, Wickner RB. Amyloids of shuffled prion domains that form prions have a parallel in-register beta-sheet structure. Biochemistry. 2008;47:4000–4007
  4. Top 500 supercomputer sites [homepage on the Internet]. Top500org, c2000-2007 [updated 2007]. Available from: http://www.top500.org/.
  5. Phillips JC, Zheng G, Kumar S, Kale LV. NAMD: Biomolecular simulation on thousands of processors. In: Proceedings of the 2002 ACM/IEEE Conference on Supercomputing, Baltimore, Maryland, September 2002. Los Alamitos, California: IEEE Computer Society Press. 2002;
  6. Bertoncini C, Jung Y, Fernandez C, Hoyer W, Griesinge C, Jovin T, et al. Release of long-range tertiary interactions potentiates aggregation of natively unstructured α-synuclein. Proc Natl Acad Sci U S A. 2005;102:1430–1435
  7. Polymeropoulos M, Higgins J, Golbe LS. Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science. 1996;274:1197–1199
  8. Glasera CB, Yamin G, Vladimirm N, Uversky VN, Fink AL. Methionine oxidation, alpha-synuclein and Parkinson's disease. Biochim Biophy Acta. 2005;1703:157–169
  9. Ibáñez P, Bonnet AM, Débarges B, Lohmann E, Tison F, Pollak P, et al. Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet. 2004;364:1169–1171
  10. Moore D, West A, Dawson W, Dawson TM. Molecular pathophysiology of Parkinson's disease. Annu Rev Neurosci. 2005;28:57–87
  11. Ulmer T, Bax A, Cole N, Nussbaum R. Structure and dynamics of micelle-bound human alpha-synuclein. J Biol Chem. 2005;280:9595–9603
  12. Davidson W, Jonas A, Clayton D, George J. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 1998;273:9443–9449
  13. Uversky V, Lee H, Li J, Fink A, Lee S. Stabilization of partially folded conformation during alpha-synuclein oligomerization in both purified and cytosolic preparations. J Biol Chem. 2001;276:43495–43498
  14. Uversky V. A protein-chameleon: conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders. J Biomol Struct Dyn. 2003;21:211–234
  15. Volles M, Lansbury PJ. Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkinson's disease. Biochemistry. 2003;42:7871–7878
  16. Henriques ST, Quintas A, Bagatolli LA, Homblé F, Castanho MA. Energy-independent translocation of cell-penetrating peptides occurs without formation of pores. A biophysical study with pep-1. Mol Membr Biol. 2007;24:282–293
  17. Glabe CG. Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging. 2006;27:570–575
  18. Kalé L, Skeel R, Bhandarkar M, Brunner R, Gursoy A, Krawetz N, et al. NAMD2: greater scalability for parallel molecular dynamics. J Comp Physics. 1999;151:282–312
  19. Feller S, MacKerell A. An improved empirical potential energy function for molecular simulations of phospholipids. J Phys Chem B. 2000;104:7510–7515
  20. Gao M, Schulten K. Onset of anthrax toxin pore formation. Biophys J. 2006;90:3267–3279
  21. Shindyalov IN, Bourne PE. A database and tools for 3-D protein structure comparison and alignment using the Combinatorial Extension (CE) algorithm. Nucleic Acids Res. 2001;29:228–229
  22. Sharikov Y, Walker RC, Greenberg J, Kouznetsova V, Nigam S, Miller MA, et al. MAPAS: a tool for predicting membrane-contacting protein surfaces. Nat|Methods. 2008;5:119
  23. Law DS, Ten Eyck LF, Katzenelson O, Tsigelny I, Roberts VA, Pique ME, et al. Finding needles in haystacks: reranking DOT results by using shape complementarity, cluster analysis, and biological information. Proteins. 2003;52:33–40
  24. Ritchie DW, Kemp GJL. Protein docking using spherical polar Fourier correlations. Proteins. 2000;39:178–194
  25. Weaver TM. The pi-helix translates structure into function. Protein Sci. 2000;9:201–206
  26. Flock D, Colacino S, Giorgio C, Di Nola A. Misfolding of the amyloid beta protein: a molecular dynamics study. Proteins. 2006;62:183–192
  27. Tsigelny IF, Bar-On P, Sharikov Y, Crews L, Hashimoto M, Miller MA, et al. Dynamics of alpha-synuclein aggregation and inhibition of pore-like oligomer development by beta-synuclein. FEBS J. 2007;274:1862–1877
  28. Furukawa K, Matsuzaki-Kobayashi M, Hasegawa T, Kikuchi A, Sugeno N, Itoyama Y, et al. Plasma membrane ion permeability induced by mutant alpha-synuclein contributes to the degeneration of neural cells. J Neurochem. 2006;97:1071–1077

 This work was supported by National Institutes of Health grants AG18440 and AG02074, and a US Department of Energy INCITE grant. The authors are also grateful to International Business Machines for funding under its Institutes of Innovation program and for computational support on its BlueGene computers at the San Diego Supercomputer Center and at the Argonne National Laboratory. Material written in this article does not have any commercial associations, current and within the past five years, that might pose a potential, perceived or real conflict of interest.

PII: S1549-9634(08)00087-7

doi: 10.1016/j.nano.2008.05.005

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 350-357 , December 2008

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