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 Aβ(10-42) as the query in the Protein Data-Bank (PDB) revealed that an RNA binding protein, AF-Sml from Archaeoglobus fulgidus (PDB entry: 1i4k chain Z), shared 36% identical residues. Using AF-Sml as a template, we built a molecular model of Aβ(10-42) by applying comparative modeling methods. The model of Aβ(10-42) 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-Sml crystal structure were found to be conserved in A. 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-Sml, RNA interacts with Aβ in the β-hairpin (β-turn-β) structure and prevents fibril formation. (C) 2005 Elsevier Inc. All rights reserved.