2L53

Solution NMR Structure of apo-calmodulin in complex with the IQ motif of Human Cardiac Sodium Channel NaV1.5

Summary for 2L53

• Entry DOI: 10.2210/pdb2l53/pdb
• Related: 2ix7
• NMR Information: BMRB: 17264
• Descriptor: Calmodulin, Voltage-gated sodium channel type V alpha isoform b variant (2 entities in total)
• Functional Keywords: calmodulin, iq motif, complex, ca-binding protein, ca-binding protein-proton transport complex, ca-binding protein/proton transport
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62158; Membrane; Multi-pass membrane protein (By similarity): Q59H93
• Total number of polymer chains: 2
• Total formula weight: 20250.46

Authors

Chagot, B.,Chazin, W.J. (deposition date: 2010-10-24, release date: 2011-01-05, Last modification date: 2024-05-01)

Primary citation

Chagot, B.,Chazin, W.J.
Solution NMR Structure of Apo-Calmodulin in Complex with the IQ Motif of Human Cardiac Sodium Channel NaV1.5.
J.Mol.Biol., 406:106-119, 2011

PubMed Abstract: The function of the human voltage-gated sodium channel Na(V)1.5 is regulated in part by intracellular calcium signals. The ubiquitous calcium sensor protein calmodulin (CaM) is an important part of the complex calcium-sensing apparatus in Na(V)1.5. CaM interacts with an IQ (isoleucine-glutamine) motif in the large intracellular C-terminal domain of the channel. Using co-expression and co-purification, we have been able to isolate a CaM-IQ motif complex and to determine its high-resolution structure in absence of calcium using multi-dimensional solution NMR. Under these conditions, the Na(V)1.5 IQ motif interacts with the C-terminal domain (C-lobe) of CaM, with the N-terminal domain remaining free in solution. The structure reveals that the C-lobe adopts a semi-open conformation with the IQ motif bound in a narrow hydrophobic groove. Sequence similarities between voltage-gated sodium channels and voltage-gated calcium channels suggest that the structure of the CaM-Na(V)1.5 IQ motif complex can serve as a general model for the interaction between CaM and ion channel IQ motifs under low-calcium conditions. The structure also provides insight into the biochemical basis for disease-associated mutations that map to the IQ motif in Na(V)1.5.

PubMed: 21167176
DOI: 10.1016/j.jmb.2010.11.046

Experimental method

SOLUTION NMR