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PDBsum entry 2ii2
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Metal binding protein
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PDB id
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2ii2
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References listed in PDB file
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Key reference
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Title
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Apo and calcium-Bound crystal structures of alpha-11 giardin, An unusual annexin from giardia lamblia.
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Authors
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P.Pathuri,
E.T.Nguyen,
S.G.Svärd,
H.Luecke.
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Ref.
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J Mol Biol, 2007,
368,
493-508.
[DOI no: ]
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PubMed id
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Abstract
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Alpha-11 giardin is a member of the multi-gene alpha-giardin family in the
intestinal protozoan, Giardia lamblia. This gene family shares an ancestry with
the annexin super family, whose common characteristic is calcium-dependent
binding to membranes that contain acidic phospholipids. Several alpha giardins
are highly expressed during parasite-induced diarrhea in humans. Despite being a
member of a large family of proteins, little is known about the function and
cellular localization of alpha-11 giardin, although giardins are often
associated with the cytoskeleton. It has been shown that Giardia exhibits high
levels of alpha-11 giardin mRNA transcript throughout its life cycle; however,
constitutive over-expression of this protein is lethal to the parasite.
Determining the three-dimensional structure of an alpha-giardin is essential to
identifying functional domains shared in the alpha-giardin family. Here we
report the crystal structures of the apo and Ca(2+)-bound forms of alpha-11
giardin, the first alpha giardin to be characterized structurally. Crystals of
apo and Ca(2+)-bound alpha-11 giardin diffracted to 1.1 A and 2.93 A,
respectively. The crystal structure of selenium-substituted apo alpha-11 giardin
reveals a planar array of four tandem repeats of predominantly alpha-helical
domains, reminiscent of previously determined annexin structures, making this
the highest-resolution structure of an annexin to date. The apo alpha-11 giardin
structure also reveals a hydrophobic core formed between repeats I/IV and
II/III, a region typically hydrophilic in other annexins. Surprisingly, the
Ca(2+)-bound structure contains only a single calcium ion, located in the DE
loop of repeat I and coordinated differently from the two types of calcium sites
observed in previous annexin structures. The apo and Ca(2+)-bound alpha-11
giardin structures assume overall similar conformations; however, Ca(2+)-bound
alpha-11 giardin crystallized in a lower-symmetry space group with four
molecules in the asymmetric unit. Vesicle-binding studies suggest that alpha-11
giardin, unlike most other annexins, does not bind to vesicles composed of
acidic phospholipids in a calcium-dependent manner.
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Figure 7.
Figure 7. Overlay of alpha-11 giardin (blue) and annexin A4
(orange) crystal structures. (a) Side view of the structure and
(b) top view from the convex side. The N termini (Nt) of
alpha-11 giardin and annexin A4 are labeled in their respective
colors. Superposition of the alpha-11 giardin and annexin A4
structures was performed in Coot^39 and the Figures were
produced with the molecular graphics program Pymol
[http://pymol.sourceforge.net/].
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Figure 8.
Figure 8. Arrangement of the four monomers in the asymmetric
unit of Ca^2+-bound alpha-11 giardin. Monomer A is shown in
yellow, monomer B in purple, monomer C in green and monomer D in
teal. Calcium ions bound to the DE loop of repeat I in each of
the four monomers are illustrated as red spheres. The Figure was
prepared with the molecular graphics program Pymol
[http://pymol.sourceforge.net/].
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
368,
493-508)
copyright 2007.
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