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PDBsum entry 2on9
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Protein fibril
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PDB id
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2on9
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References listed in PDB file
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Key reference
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Title
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Atomic structures of amyloid cross-Beta spines reveal varied steric zippers.
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Authors
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M.R.Sawaya,
S.Sambashivan,
R.Nelson,
M.I.Ivanova,
S.A.Sievers,
M.I.Apostol,
M.J.Thompson,
M.Balbirnie,
J.J.Wiltzius,
H.T.Mcfarlane,
A.Ã.˜.Madsen,
C.Riekel,
D.Eisenberg.
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Ref.
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Nature, 2007,
447,
453-457.
[DOI no: ]
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PubMed id
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Abstract
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Amyloid fibrils formed from different proteins, each associated with a
particular disease, contain a common cross-beta spine. The atomic architecture
of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein
Sup35, was recently revealed by X-ray microcrystallography. It is a pair of
beta-sheets, with the facing side chains of the two sheets interdigitated in a
dry 'steric zipper'. Here we report some 30 other segments from fibril-forming
proteins that form amyloid-like fibrils, microcrystals, or usually both. These
include segments from the Alzheimer's amyloid-beta and tau proteins, the PrP
prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin,
alpha-synuclein and beta(2)-microglobulin, suggesting that common structural
features are shared by amyloid diseases at the molecular level. Structures of 13
of these microcrystals all reveal steric zippers, but with variations that
expand the range of atomic architectures for amyloid-like fibrils and offer an
atomic-level hypothesis for the basis of prion strains.
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Figure 2.
Figure 2: Thirteen atomic-resolution structures for peptide
segments of fibril-forming proteins. See text for details
of nomenclature. A two-sheet motif of each structure is depicted
in projection down the needle crystal axis, showing only the top
members of  10^5
stacked segments in each crystalline sheet. A dry, steric-zipper
interaction is evidenced by the interdigitation of side chains
between sheets. Carbon atoms are shown as purple or white,
nitrogen as blue, and oxygen as red. Water molecules are shown
as yellow spheres. NNQQNY also contains zinc acetate. Zippers
are grouped by class (1, 2, 4, 7, 8); see text for details.
Previously reported Sup35 zippers^22 belong to class 1. The
three pairs of structures related by blue double-headed arrows
are polymorphic pairs (forms 1 and 2; see text for details). The
red arrows point to the 90° bend in the upper sheet of
MVGGVV form 2.
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Figure 4.
Figure 4: The eight classes of steric zippers. Two identical
sheets can be classified by: the orientation of their faces
(either 'face-to-face' or 'face-to-back'), the orientation of
their strands (with both sheets having the same edge of the
strand 'up', or one 'up' and the other 'down'), and whether the
strands within the sheets are parallel or antiparallel. Both
side views (left) and top views (right) show which of the six
residues of the segment point into the zipper and which point
outward. Green arrows show two-fold screw axes, and yellow
arrows show translational symmetry. Below each class are listed
protein segments that belong to that class.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2007,
447,
453-457)
copyright 2007.
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Headers
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