Structural highlights
Function
[CALM_PARTE] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. [SCN2A_RAT] Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Publication Abstract from PubMed
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 (Ca2+)4-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca2+)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 (Ca2+)2-CaMC bound to NaV1.2IQp. The polarity of (Ca2+)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.
Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2.,Hovey L, Fowler CA, Mahling R, Lin Z, Miller MS, Marx DC, Yoder JB, Kim EH, Tefft KM, Waite BC, Feldkamp MD, Yu L, Shea MA Biophys Chem. 2017 Mar 9;224:1-19. doi: 10.1016/j.bpc.2017.02.006. PMID:28343066[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hovey L, Fowler CA, Mahling R, Lin Z, Miller MS, Marx DC, Yoder JB, Kim EH, Tefft KM, Waite BC, Feldkamp MD, Yu L, Shea MA. Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel NaV1.2. Biophys Chem. 2017 Mar 9;224:1-19. doi: 10.1016/j.bpc.2017.02.006. PMID:28343066 doi:https://dx.doi.org/10.1016/j.bpc.2017.02.006
