2nnt: Difference between revisions

Revision as of 09:40, 4 May 2008

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 Page seeded by OCA on Sun May 4 09:40:52 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2nnt.gif|left|200px]]
- {{Structure
+<!--
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+The line below this paragraph, containing "STRUCTURE_2nnt", creates the "Structure Box" on the page.
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-|GENE= TCERG1, CA150, TAF2S ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2nnt|  PDB=2nnt  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2nnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nnt OCA], [http://www.ebi.ac.uk/pdbsum/2nnt PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2nnt RCSB]</span>
-}}
 '''General structural motifs of amyloid protofilaments'''
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 [[Category: Tidow, H.]]
 [[Category: Tremmel, S.]]
-[[Category: beta-hairpin]]
+[[Category: Beta-hairpin]]
-[[Category: ca150 second ww domain]]
+[[Category: Ca150 second ww domain]]
-[[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 Mar 31 04:05:40 2008''