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* Residue conservation analysis
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DOI no:
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Structure
14:1547-1556
(2006)
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PubMed id:
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Complex of calmodulin with a ryanodine receptor target reveals a novel, flexible binding mode.
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A.A.Maximciuc,
J.A.Putkey,
Y.Shamoo,
K.R.Mackenzie.
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ABSTRACT
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Calmodulin regulates ryanodine receptor-mediated Ca(2+) release through a
conserved binding site. The crystal structure of Ca(2+)-calmodulin bound to this
conserved site reveals that calmodulin recognizes two hydrophobic anchor
residues at a novel "1-17" spacing that brings the calmodulin lobes
close together but prevents them from contacting one another. NMR residual
dipolar couplings demonstrate that the detailed structure of each lobe is
preserved in solution but also show that the lobes experience domain motions
within the complex. FRET measurements confirm the close approach of the lobes in
binding the 1-17 target and show that calmodulin binds with one lobe to a
peptide lacking the second anchor. We suggest that calmodulin regulates the
Ca(2+) channel by switching between the contiguous binding mode seen in our
crystal structure and a state where one lobe of calmodulin contacts the
conserved binding site while the other interacts with a noncontiguous site on
the channel.
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Selected figure(s)
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Figure 1.
Figure 1. The RYR1 Target Presents Hydrophobic Anchors on
Opposite Faces of a Helix
(A) Alignment of CaM binding-site
residues 3614–3643 of human RYR1 with rat and zebrafish RYR1
sequences and human RYR2 and RYR3 sequences. Residues identical
in at least four sequences are in boldface.
(B) Electron
density for the target peptide is well defined. Stereo pair of
electron density from the final 2F[o] − F[c] composite omit
map, contoured at 1.5 σ, at the target peptide
(Trp3621–Arg3630). The final model is superimposed on the map.
(C) The 1-17 anchor spacing positions the lobes of CaM on
opposite sides of the helical target. Two views of a ribbon
diagram representation of the Ca^2+CaM/RYR1 peptide complex. CaM
is drawn in blue, the RYR1 peptide in white, and the four
calcium atoms are shown in red. The side chains of the RYR1
hydrophobic residues that anchor the two lobes of CaM are shown
as sticks. Images were generated in PyMOL (DeLano Scientific).
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Figure 3.
Figure 3. Local Interactions between CaM Lobes and RYR1
Anchors Are Similar to the CaM/smMLCK Complex
Superposition
of the Cα atoms of (A) the C lobe of CaM (residues 84 to 146)
and (B) the N lobe of CaM (residues 5 to 75) from the RYR1 and
smMLCK complexes. Only the hydrophobic anchors of the peptides
(Trp3620 and Phe3636 in RYR1, Trp800 and Leu813 in smMLCK) and
the CaM residues that interact with them are shown. For the RYR1
complex, the peptide chain is drawn as a white ribbon, with the
anchors shown as thick sticks, while the CaM residues are shown
as sticks, with the carbon atoms colored in blue, nitrogen in
slate, oxygen in red, and sulfur in orange. The peptide chain
for smMLCK is shown in cyan, and residues from the CaM/smMLCK
complex are represented as thin sticks.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2006,
14,
1547-1556)
copyright 2006.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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D.W.Song,
J.G.Lee,
H.S.Youn,
S.H.Eom,
and
d.o. .H.Kim
(2011).
Ryanodine receptor assembly: A novel systems biology approach to 3D mapping.
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Prog Biophys Mol Biol,
105,
145-161.
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E.Kovacs,
J.Tóth,
B.G.Vértessy,
and
K.Liliom
(2010).
Dissociation of calmodulin-target peptide complexes by the lipid mediator sphingosylphosphorylcholine: implications in calcium signaling.
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J Biol Chem,
285,
1799-1808.
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E.Y.Kim,
C.H.Rumpf,
F.Van Petegem,
R.J.Arant,
F.Findeisen,
E.S.Cooley,
E.Y.Isacoff,
and
D.L.Minor
(2010).
Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.
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EMBO J,
29,
3924-3938.
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PDB code:
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J.Jiang,
Y.Zhou,
J.Zou,
Y.Chen,
P.Patel,
J.J.Yang,
and
E.M.Balog
(2010).
Site-specific modification of calmodulin Ca²(+) affinity tunes the skeletal muscle ryanodine receptor activation profile.
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Biochem J,
432,
89-99.
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N.Juranic,
E.Atanasova,
A.G.Filoteo,
S.Macura,
F.G.Prendergast,
J.T.Penniston,
and
E.E.Strehler
(2010).
Calmodulin wraps around its binding domain in the plasma membrane Ca2+ pump anchored by a novel 18-1 motif.
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J Biol Chem,
285,
4015-4024.
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PDB code:
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G.Meissner,
D.A.Pasek,
N.Yamaguchi,
S.Ramachandran,
N.V.Dokholyan,
and
A.Tripathy
(2009).
Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine receptor ion channels.
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Proteins,
74,
207-211.
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H.Ishida,
M.Rainaldi,
and
H.J.Vogel
(2009).
Structural studies of soybean calmodulin isoform 4 bound to the calmodulin-binding domain of tobacco mitogen-activated protein kinase phosphatase-1 provide insights into a sequential target binding mode.
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J Biol Chem,
284,
28292-28305.
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PDB code:
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P.A.Lobo,
and
F.Van Petegem
(2009).
Crystal structures of the N-terminal domains of cardiac and skeletal muscle ryanodine receptors: insights into disease mutations.
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Structure,
17,
1505-1514.
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PDB codes:
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R.L.Cornea,
F.Nitu,
S.Gruber,
K.Kohler,
M.Satzer,
D.D.Thomas,
and
B.R.Fruen
(2009).
FRET-based mapping of calmodulin bound to the RyR1 Ca2+ release channel.
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Proc Natl Acad Sci U S A,
106,
6128-6133.
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N.T.Wright,
B.L.Prosser,
K.M.Varney,
D.B.Zimmer,
M.F.Schneider,
and
D.J.Weber
(2008).
S100A1 and calmodulin compete for the same binding site on ryanodine receptor.
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J Biol Chem,
283,
26676-26683.
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PDB code:
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A.P.Yamniuk,
M.Rainaldi,
and
H.J.Vogel
(2007).
Calmodulin has the Potential to Function as a Ca-Dependent Adaptor Protein.
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Plant Signal Behav,
2,
354-357.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
