2nnt
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General structural motifs of amyloid protofilaments
OverviewOverview
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.
About this StructureAbout this Structure
2NNT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
General structural motifs of amyloid protofilaments., Ferguson N, Becker J, Tidow H, Tremmel S, Sharpe TD, Krause G, Flinders J, Petrovich M, Berriman J, Oschkinat H, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16248-53. Epub 2006 Oct 23. PMID:17060612
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