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Structural Convergence Among Diverse, Toxic beta-Sheet Ion Channels

  1. Author:
    Jang, H.
    Arce, F. T.
    Ramachandran, S.
    Capone, R.
    Lal, R.
    Nussinov, R.

  2. Author Address

    [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.;Lal, R, Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.;rlal@ucsd.edu ruthnu@helix.nih.gov
    1. Year: 2010
    2. Date: Jul 29
    3. Epub Date: 7/9/2010
  2. Journal: Journal of Physical Chemistry B
    1. 114
    2. 29
    3. Pages: 9445-9451
  4. Type of Article: Article
  5. ISSN: 1520-6106
  1. Abstract:

    Recent studies show that an array of beta-sheet peptides, including N-terminally truncated A beta peptides (A beta(11-42/17-42)), K3 (a beta(2)-microglobulin fragment), and protegrin-1 (PG-1) peptides form ion channel-like structures and elicit single channel ion conductance when reconstituted in lipid bilayers and induce cell damage through cell calcium overload. Striking similarities are observed in the dimensions of these toxic channels irrespective of their amino acid sequences. However, the intriguing question of preferred channel sizes is still unresolved. Here, exploiting ssNMR-based, U-shaped, beta-strand-turn-beta-strand coordinates, we modeled truncated A beta peptide (p3) channels with different sizes (12- to 36-mer). Molecular dynamics (MD) simulations show that optimal channel sizes of the ion channels presenting toxic ionic flux range between 16- and 24-mer. This observation is in good agreement with channel dimensions imaged by AFM for A beta(9-42), K3 fragment, and PG-1 channels and highlights the bilayer-supported preferred toxic beta-channel sizes and organization, regardless of the peptide sequence.

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External Sources

  1. View Full Text
  2. DOI: 10.1021/jp104073k
  3. PMID: 20608696
  4. PMCID: PMC2908347
  5. View record in Web of Science®
  6. WOS: 000280071400014

Library Notes

  1. Fiscal Year: FY2009-2010
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