Biochem Biophys Res Commun. 2005 Jul 1;332(2):585-92.
Model of
Alzheimer's disease amyloid-beta peptide based on a
RNA binding protein.
Mathura VS, Paris D, Ait-Ghezala G,
Quadros A, Patel NS, Kolippakkam D,
Volmar CH, Mullan MJ.
Roskamp Institute,
Although Alzheimer's Abeta peptide has been shown to
form beta-sheet structure, a high-resolution molecular structure is still
unavailable to date. A search for a sequence neighbor using Abeta(10-42) 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 Abeta(10-42) by applying comparative modeling methods. The model
of Abeta(10-42)
contains an antiparallel beta-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 Abeta.
Using a native gel we demonstrate for the first time that RNA can interact with
Abeta and selectively retard the formation of fibrils
or higher-order oligomers. We hypothesize that in a
similar fashion to AF-Sm1, RNA interacts with Abeta in the beta-hairpin (beta-turn-beta) structure and
prevents fibril formation.
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Keywords: Alzheimers disease, amyloid-beta, RNA binding protein, Biochemical and Biophysical Research Communications