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PDBsum entry 2v17
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Immune system
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PDB id
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2v17
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References listed in PDB file
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Key reference
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Title
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X-Ray structure of the phf core c-Terminus: insight into the folding of the intrinsically disordered protein tau in alzheimer'S disease.
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Authors
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J.Sevcik,
R.Skrabana,
R.Dvorsky,
N.Csokova,
K.Iqbal,
M.Novak.
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Ref.
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Febs Lett, 2007,
581,
5872-5878.
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PubMed id
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Abstract
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The major constituent of Alzheimer's disease paired helical filaments (PHF) core
is intrinsically disordered protein (IDP) tau. In spite of a considerable
effort, insoluble character of PHF together with inherent physical properties of
IDP tau have precluded so far reconstruction of PHF 3D structure by X-ray
crystallography or NMR spectroscopy. Here we present first crystallographic
study of PHF core C-terminus. Using monoclonal antibody MN423 specific to the
tertiary structure of the PHF core, the in vivo PHF structure was imprinted into
recombinant core PHF tau. Crystallization of the complex led to determination of
the structure of the core PHF tau protein fragment 386TDHGAE391 at 1.65A
resolution. Structural analysis suggests important role of the core PHF
C-terminus for PHF assembly. It is reasonable to expect that this approach will
help to reveal the structural principles underlying the tau protein assembly
into PHF and possibly will facilitate rationale drug design for inhibition of
Alzheimer neurofibrillary changes.
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