Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10768538 | Biochemical and Biophysical Research Communications | 2005 | 8 Pages |
Abstract
Although Alzheimer's Aβ peptide has been shown to form β-sheet structure, a high-resolution molecular structure is still unavailable to date. A search for a sequence neighbor using Aβ10-42 as the query in the Protein Data-Bank (PDB) revealed that an RNA binding protein, AF-Sm1 from Archaeoglobus fulgidus (PDB entry: 1i4k chain Z), shared 36% identical residues. Using AF-Sm1 as a template, we built a molecular model of Aβ10-42 by applying comparative modeling methods. The model of Aβ10-42 contains an antiparallel β-sheet formed by residues 16-23 and 32-41. Hydrophobic surface constituted by residues 17-20 (LVFF) separates distinctly charged regions. Residues that interact with RNA in the AF-Sm1 crystal structure were found to be conserved in Aβ. Using a native gel we demonstrate for the first time that RNA can interact with Aβ and selectively retard the formation of fibrils or higher-order oligomers. We hypothesize that in a similar fashion to AF-Sm1, RNA interacts with Aβ in the β-hairpin (β-turn-β) structure and prevents fibril formation.
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Authors
Venkatarajan S. Mathura, Daniel Paris, Ghania Ait-Ghezala, Amita Quadros, Nikunj S. Patel, Deepak N. Kolippakkam, Claude-Henry Volmar, Michael J. Mullan,