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PDBsum entry 2jc2
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Metal binding protein
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PDB id
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2jc2
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References listed in PDB file
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Key reference
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Title
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Molecular basis for the impaired function of the natural f112l sorcin mutant: X-Ray crystal structure, Calcium affinity, And interaction with annexin VII and the ryanodine receptor.
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Authors
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S.Franceschini,
A.Ilari,
D.Verzili,
C.Zamparelli,
A.Antaramian,
A.Rueda,
H.H.Valdivia,
E.Chiancone,
G.Colotti.
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Ref.
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Faseb J, 2008,
22,
295-306.
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PubMed id
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Abstract
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The penta-EF hand protein sorcin participates in the modulation of Ca2+-induced
calcium-release in the heart through the interaction with several Ca2+ channels
such as the ryanodine receptor. The modulating activity is impaired in the
recently described natural F112L mutant. The F112 residue is located at the end
of the D helix next to Asp113, one of the calcium ligands in the EF3 hand
endowed with the highest affinity for the metal. The F112L-sorcin X-ray crystal
structure at 2.5 A resolution displays marked alterations in the EF3 hand, where
the hydrogen bonding network established by Phe112 is disrupted, and in the EF1
region, which is tilted in both monomers that give rise to the dimer, the stable
form of the molecule. In turn, the observed tilt is indicative of an increased
flexibility of the N-terminal part of the molecule. The structural alterations
result in a 6-fold decrease in calcium affinity with respect to the wild-type
protein and to an even larger impairment of the interaction with annexin VII and
of the ability of sorcin to interact with and inhibit ryanodine receptors. These
results provide a plausible structural and functional framework that helps
elucidate the phenotypic alterations of mice overexpressing F112L-sorcin.
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Secondary reference #1
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Title
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The crystal structure of the sorcin calcium binding domain provides a model of ca2+-Dependent processes in the full-Length protein.
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Authors
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A.Ilari,
K.A.Johnson,
V.Nastopoulos,
D.Verzili,
C.Zamparelli,
G.Colotti,
D.Tsernoglou,
E.Chiancone.
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Ref.
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J Mol Biol, 2002,
317,
447-458.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. SCBD monomer. In (a) the eight a-helices are
labelled. In (b) and c) a comparison with the grancalcin and
calpain monomers in the apo- (b) and calcium-bound form (c) is
shown. SCBD is coloured red, grancalcin green and calpain blue.
In (c) the three calcium ions bound to calpain are depicted. The
pictures were prepared with the program MOLSCRIPT.[33]
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Figure 3.
Figure 3. (a) SCBD dimer. The two different monomers are
depicted in different colours and the residues buried upon dimer
formation are indicated. (b) Tetrameric interface. B and D are
the interacting monomers. (c) Blow up of the tetrameric
interface. The residues buried upon tetramer formation are
indicated. The pictures were prepared with the program
MOLSCRIPT.[33]
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #2
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Title
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Crystal structure of calcium-Free human sorcin: a member of the penta-Ef-Hand protein family.
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Authors
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X.Xie,
M.D.Dwyer,
L.Swenson,
M.H.Parker,
M.C.Botfield.
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Ref.
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Protein Sci, 2001,
10,
2419-2425.
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PubMed id
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