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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2005-5-24
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
332
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
585-92
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15896718-Amino Acid Sequence,
pubmed-meshheading:15896718-Amyloid beta-Peptides,
pubmed-meshheading:15896718-Archaeal Proteins,
pubmed-meshheading:15896718-Binding Sites,
pubmed-meshheading:15896718-Computer Simulation,
pubmed-meshheading:15896718-Dimerization,
pubmed-meshheading:15896718-Models, Chemical,
pubmed-meshheading:15896718-Models, Molecular,
pubmed-meshheading:15896718-Molecular Sequence Data,
pubmed-meshheading:15896718-Multiprotein Complexes,
pubmed-meshheading:15896718-Protein Binding,
pubmed-meshheading:15896718-Protein Conformation,
pubmed-meshheading:15896718-RNA-Binding Proteins,
pubmed-meshheading:15896718-Ribonucleoproteins, Small Nuclear,
pubmed-meshheading:15896718-Sequence Analysis, Protein,
pubmed-meshheading:15896718-Sequence Homology, Amino Acid
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pubmed:year |
2005
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pubmed:articleTitle |
Model of Alzheimer's disease amyloid-beta peptide based on a RNA binding protein.
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pubmed:affiliation |
Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. venkat@rfdn.org
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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