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| [[Image:2nnt.gif|left|200px]] | | {{Seed}} |
| | [[Image:2nnt.png|left|200px]] |
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| {{STRUCTURE_2nnt| PDB=2nnt | SCENE= }} | | {{STRUCTURE_2nnt| PDB=2nnt | SCENE= }} |
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| '''General structural motifs of amyloid protofilaments'''
| | ===General structural motifs of amyloid protofilaments=== |
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| ==Overview==
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| Human CA150, a transcriptional activator, binds to and is co-deposited with huntingtin during Huntington's disease. The second WW domain of CA150 is a three-stranded beta-sheet that folds in vitro in microseconds and forms amyloid fibers under physiological conditions. We found from exhaustive alanine scanning studies that fibrillation of this WW domain begins from its denatured conformations, and we identified a subset of residues critical for fibril formation. We used high-resolution magic-angle-spinning NMR studies on site-specific isotopically labeled fibrils to identify abundant long-range interactions between side chains. The distribution of critical residues identified by the alanine scanning and NMR spectroscopy, along with the electron microscopy data, revealed the protofilament repeat unit: a 26-residue non-native beta-hairpin. The structure we report has similarities to the hairpin formed by the A(beta)((1-40)) protofilament, yet also contains closely packed side-chains in a "steric zipper" arrangement found in the cross-beta spine formed from small peptides from the Sup35 prion protein. Fibrillation of unrelated amyloidogenic sequences shows the common feature of zippered repeat units that act as templates for fiber elongation.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17060612}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17060612 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17060612}} |
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| ==About this Structure== | | ==About this Structure== |
| 2NNT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NNT OCA]. | | 2NNT is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NNT OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Fbp28 protofilament]] | | [[Category: Fbp28 protofilament]] |
| [[Category: Fibre]] | | [[Category: Fibre]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:40:52 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:34:22 2008'' |