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PDBsum entry 2be4
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Structural genomics, unknown function
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PDB id
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2be4
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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 danio rerio secretagogin: a hexa-Ef-Hand calcium sensor.
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Authors
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E.Bitto,
C.A.Bingman,
L.Bittova,
R.O.Frederick,
B.G.Fox,
G.N.Phillips.
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Ref.
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Proteins, 2009,
76,
477-483.
[DOI no: ]
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PubMed id
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Abstract
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Many essential physiological processes are regulated by the modulation of
calcium concentration in the cell. The EF-hand proteins represent a superfamily
of calcium-binding proteins involved in calcium signaling and homeostasis.
Secretagogin is a hexa-EF-hand protein that is highly expressed in pancreatic
islet of Langerhans and neuroendocrine cells and may play a role in the
trafficking of secretory granules. We present the X-ray structure of Danio rerio
secretagogin, which is 73% identical to human secretagogin, in calcium-free form
at 2.1-A resolution. Secretagogin consists of the three globular domains each of
which contains a pair of EF-hand motifs. The domains are arranged into a
V-shaped molecule with a distinct groove formed at the interface of the domains.
Comparison of the secretagogin structure with the solution structure of
calcium-loaded calbindin D(28K) revealed a striking difference in the spatial
arrangement of their domains, which involves approximately 180 degrees rotation
of the first globular domain with respect to the module formed by the remaining
domains. Proteins 2009. (c) 2009 Wiley-Liss, Inc.
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Figure 1.
Figure 1. The X-ray crystal structure of D. rerio secretagogin.
A: Secretagogin monomer consists of six EF-hand motifs arranged
in pairs to form three globular domains (rendered consecutively
in red, yellow, and cyan). Linkers L1 and L2, highlighted in
green, connect the individual domains. The apposed metal binding
loops form antiparallel  -sheet
on the outer surface of the V-shaped molecule. The helices of
the individual EF-hand motifs are labeled for clarity. B: A
stereo view of C  -trace
of the superposed domains I, II, and III (red, yellow, and cyan,
respectively) of secretagogin. The topologically equivalent
motifs EF1, EF3, and EF5 overlap well, except for the
Ca^2+-binding loop which adopts the open,  Ca^2+-ready
 conformation
in EF5-hand (cyan arrow) and closed, Ca^2+-free
conformation
in EF1 and EF3 motifs. The EF2 hand differs from all the
remaining EF-hands due to a break at Met63 in the helix E2 (red
arrow). C: A stereo image of the calcium-binding loop in
EF5-hand motif of D. rerio secretagogin. A final 2mF[o]-DF[c]
electron density map (blue mesh) is contoured at 1.2  level.
The refined protein model is shown in sticks. Residues of the
calcium-binding motif at positions 1 (Asp206), 3 (Ser208), 5
(Thr210), 7 (Ala212), and 12 (Glu217) are labeled for clarity. A
symmetry molecule of secretagogin from the crystalline lattice
contributes Lys138 (cyan sticks), which mimics the positively
charged calcium ion and stabilizes the loop in Ca^2+-ready
-like
conformation.
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Figure 3.
Figure 3. D. rerio secretagogin and rat calbindin D[28K] have
different quarternary domain arrangement. The domain II and III
of D. rerio secretagogin (red) were superposed with the
corresponding region of rat calbindin D[28K] (blue; PDB ID
2f33). In the resulting overlay, the domain I of secretagogin is
rotated by almost 180° with respect to the core formed by
domains II and III in both proteins. The green arrow points to
the point from which structures diverge.
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The above figures are
reprinted
from an Open Access publication published by John Wiley & Sons, Inc.:
Proteins
(2009,
76,
477-483)
copyright 2009.
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