2M5E

Structure of the C-domain of Calcium-saturated Calmodulin bound to the IQ motif of NaV1.2

Summary for 2M5E

• Entry DOI: 10.2210/pdb2m5e/pdb
• Related: 1EXR 2KXW
• NMR Information: BMRB: 19050
• Descriptor: Calmodulin, Sodium channel protein type 2 subunit alpha, CALCIUM ION (3 entities in total)
• Functional Keywords: calcium binding protein, nav1.2, ion channel gating, iq motif, metal binding, sodium channels, metal transport, voltage dependent, voltage gated, calcium binding protein-metal transport complex, neuronal peptides, ef-hand, calcium-binding protein-metal transport complex, calcium-binding protein/metal transport
• Biological source: Paramecium tetraurelia; More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P04775
• Total number of polymer chains: 2
• Total formula weight: 11866.56

Authors

Fowler, C.A.,Feldkamp, M.D.,Yu, L.,Shea, M.A. (deposition date: 2013-02-21, release date: 2014-07-23, Last modification date: 2024-05-15)

Primary citation

Hovey, L.,Fowler, C.A.,Mahling, R.,Lin, Z.,Miller, M.S.,Marx, D.C.,Yoder, J.B.,Kim, E.H.,Tefft, K.M.,Waite, B.C.,Feldkamp, M.D.,Yu, L.,Shea, M.A.
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., 224:1-19, 2017

PubMed Abstract: Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel Na1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM. We have determined equilibrium dissociation constants for rat Na1.2 IQ motif [IQRAYRRYLLK] binding to apo CaM (~3nM) and (Ca)-CaM (~85nM), showing that apo CaM binding is favored by 30-fold. For both apo and (Ca)-CaM, NMR demonstrated that Na1.2 IQ motif peptide (Na1.2) exclusively made contacts with C-domain residues of CaM (CaM). To understand how calcium triggers conformational change at the CaM-IQ interface, we determined a solution structure (2M5E.pdb) of (Ca)-CaM bound to Na1.2. The polarity of (Ca)-CaM relative to the IQ motif was opposite to that seen in apo CaM-Na1.2 (2KXW), revealing that CaM recognizes nested, anti-parallel sites in Na1.2. Reversal of CaM may require transient release from the IQ motif during calcium binding, and facilitate a re-orientation of CaM allowing interactions with non-IQ Na1.2 residues or auxiliary regulatory proteins interacting in the vicinity of the IQ motif.

PubMed: 28343066
DOI: 10.1016/j.bpc.2017.02.006

Experimental method

SOLUTION NMR