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Title
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X-ray analysis of the eye lens protein gamma-II crystallin at 1.9 A resolution.
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Authors
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G.Wistow,
B.Turnell,
L.Summers,
C.Slingsby,
D.Moss,
L.Miller,
P.Lindley,
T.Blundell.
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Ref.
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J Mol Biol, 1983,
170,
175-202.
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PubMed id
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Abstract
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We report the X-ray structure analysis and refinement at 1.9 A resolution of
calf gamma-II crystallin, a lens-specific protein. The sequence of Croft (1972)
has been modified to give a polypeptide chain of 174 residues (cf. 165). The
protein has a symmetrical, hierarchical structure of two globular domains each
comprising two similar "Greek key" motifs, consecutive along the
polypeptide chain, and related by a pseudo 2-fold axis. The two domains pack
together with a single connection and are related by a further pseudo 2-fold
axis which bisects the angle between the intra-domain dyads. Forty-two pairs of
C alpha positions for the two most similar motifs have root-mean-square
separation at best fit of 0.69 A. The N and C-terminal domains gave
root-mean-square separation of 0.89 A for 82 pairs of C alpha atoms at best fit.
In each domain the two Greek key motifs form a pair of four-stranded
antiparallel beta-pleated sheets, each sheet composed of three stands from one
motif and one from the other. The sheets pack together in a wedge shape, closed
at the top by the loops connecting the third and fourth strands of each motif.
The first two strands of each motif form an extended beta-hairpin which is
folded on to the beta-sheet. The packing of each motif into the globular domains
involves a staggered bilayer of side-chains between each pair of beta-sheets
which does not preserve the pseudo 2-fold axes observed in the C alpha position
topology. In the core of each domain there are interactions between polarizable
aromatic groups and sulphur-containing residues which may contribute to
stability and may also serve to protect aromatic side-chains from ultraviolet
light damage in the lens. At the surface of the molecule over half the ionic
side-chains are closely paired, which probably stabilizes the tertiary fold and
may reduce the water bound. Crystal lattice interactions are described which may
be similar to those occurring in vivo in the lens between crystallins. Seven
cysteine residues have been identified in the structure and these may have a
role in the thermodynamic stability of the molecule, its intermolecular
interactions under the normal reducing conditions of the lens, and also in the
aggregation and cross-linking which occur in some forms of cataract. Three of
these residues, Cys18, Cys23 and Cys74, form a cluster in the N-terminal
domain.(ABSTRACT TRUNCATED AT 400 WORDS)
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