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PDBsum entry 2k2f
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Metal binding protein
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PDB id
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2k2f
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References listed in PDB file
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Key reference
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Title
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S100a1 and calmodulin compete for the same binding site on ryanodine receptor.
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Authors
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N.T.Wright,
B.L.Prosser,
K.M.Varney,
D.B.Zimmer,
M.F.Schneider,
D.J.Weber.
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Ref.
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J Biol Chem, 2008,
283,
26676-26683.
[DOI no: ]
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PubMed id
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Abstract
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In heart and skeletal muscle an S100 protein family member, S100A1, binds to the
ryanodine receptor (RyR) and promotes Ca(2+) release. Using competition binding
assays, we further characterized this system in skeletal muscle and showed that
Ca(2+)-S100A1 competes with Ca(2+)-calmodulin (CaM) for the same binding site on
RyR1. In addition, the NMR structure was determined for Ca(2+)-S100A1 bound to a
peptide derived from this CaM/S100A1 binding domain, a region conserved in RyR1
and RyR2 and termed RyRP12 (residues 3616-3627 in human RyR1). Examination of
the S100A1-RyRP12 complex revealed residues of the helical RyRP12 peptide
(Lys-3616, Trp-3620, Lys-3622, Leu-3623, Leu-3624, and Lys-3626) that are
involved in favorable hydrophobic and electrostatic interactions with
Ca(2+)-S100A1. These same residues were shown previously to be important for
RyR1 binding to Ca(2+)-CaM. A model for regulating muscle contraction is
presented in which Ca(2+)-S100A1 and Ca(2+)-CaM compete directly for the same
binding site on the ryanodine receptor.
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Figure 4.
FIGURE 4. Residues of the RyRP12 peptide (residues
3616-3627 or RyR1) and S100A1 involved in Ca^2^+-S100A1-RyRP12
complex formation. A, diagram illustrating hydrophobic residues
involved in the RyRP12-S100A1 interaction including Ala-53,
Ile-57, Leu-77, Ala-80, Leu-81, and Ala-84 of S100A1, and
Trp-3620, Leu-3623, and Leu-3624 of RyRP12. B, ribbon diagram
illustrating hydrophilic residues in the RyRP12-S100A1 complex
that are likely involved in ionic interactions, including Asp-52
and Glu-63 on S100A1 and Lys-3616, Lys-3622, and Lys-3627 on the
RyRP12 peptide. C, space-filling diagram of the S100A1-RyP12
peptide showing residues in green (Trp-3620 and Leu-3624) that
are important for calmodulin binding to the ryanodine receptor.
The rest of the RyRP12 peptide is colored in red, and the S100A1
subunits 1 and 2 are colored tan and blue, respectively. D,
ribbon diagram of the C-terminal region of CaM bound to the
CaMBD of the RyR (residues 3614-3643 of RyR; Protein Data Bank
code 2BCX) (17), showing side chains of the RyR that are
involved in ionic interactions with CaM; these same residues are
also likely to form salt bridges with negatively charged side
chains of Ca^2+-S100A1.
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Figure 5.
FIGURE 5. Schematic of S100A1 function in skeletal muscle.
Ca^2+-S100A1 and Ca^2+-CaM bind to an overlapping region of RyR1
(red) in a Ca^2+-dependent manner. S100A1 binding leads to
events that enhance SR calcium release. In contrast, calmodulin
binding to this CaM binding domain leads to events that reduce
SR calcium release. Competition between these two
calcium-binding proteins for this target site may regulate SR
Ca^2+ release in skeletal muscle. The asterisk close to the
Ca^2+-S100A1-RyRP12 structure denotes the location of the
residues of RyR that are C-terminal to RyRP12 (residues
3616-3627 of RyR) present in the longer RyR peptide (residues
3614-3643 of RyR), used for structural studies when bound to CaM.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2008,
283,
26676-26683)
copyright 2008.
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