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PDBsum entry 2m5e
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Calcium-binding protein/metal transport
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PDB id
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2m5e
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References listed in PDB file
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Key reference
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Title
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Calcium triggers reversal of calmodulin on nested anti-Parallel sites in the iq motif of the neuronal voltage-Dependent sodium channel nav1.2.
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Authors
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L.Hovey,
C.A.Fowler,
R.Mahling,
Z.Lin,
M.S.Miller,
D.C.Marx,
J.B.Yoder,
E.H.Kim,
K.M.Tefft,
B.C.Waite,
M.D.Feldkamp,
L.Yu,
M.A.Shea.
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Ref.
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Biophys Chem, 2017,
224,
1.
[DOI no: ]
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PubMed id
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Abstract
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Several members of the voltage-gated sodium channel family are regulated by
calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel
NaV1.2 contains binding sites for both apo (calcium-depleted) and
calcium-saturated CaM. We have determined equilibrium dissociation constants for
rat NaV1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca(2+))4-CaM
(~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and
(Ca(2+))4-CaM, NMR demonstrated that NaV1.2 IQ motif peptide (NaV1.2IQp)
exclusively made contacts with C-domain residues of CaM (CaMC). To understand
how calcium triggers conformational change at the CaM-IQ interface, we
determined a solution structure (2M5E.pdb) of (Ca(2+))2-CaMC bound to NaV1.2IQp.
The polarity of (Ca(2+))2-CaMC relative to the IQ motif was opposite to that
seen in apo CaMC-Nav1.2IQp (2KXW), revealing that CaMC recognizes nested,
anti-parallel sites in Nav1.2IQp. Reversal of CaM may require transient release
from the IQ motif during calcium binding, and facilitate a re-orientation of
CaMN allowing interactions with non-IQ NaV1.2 residues or auxiliary regulatory
proteins interacting in the vicinity of the IQ motif.
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Secondary reference #1
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Title
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Structural and energetic determinants of apo calmodul binding to the iq motif of the nav1.2 voltage-Depende sodium channel
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Authors
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M.D.Feldkamp,
L.Yu,
M.A.Shea.
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Ref.
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structure, 2011,
19,
733.
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