Journal article
Backbone resonance assignments of complexes of apo human calmodulin bound to IQ motif peptides of voltage-dependent sodium channels NaV1.1, NaV1.4 and NaV1.7
Biomolecular NMR assignments, Vol.12(2), pp.283-289
10/2018
DOI: 10.1007/s12104-018-9824-5
PMCID: PMC6274588
PMID: 29728980
Abstract
Human voltage-gated sodium (NaV) channels are critical for initiating and propagating action potentials in excitable cells. Nine isoforms have different roles but similar topologies, with a pore-forming α-subunit and auxiliary transmembrane β-subunits. NaV pathologies lead to debilitating conditions including epilepsy, chronic pain, cardiac arrhythmias, and skeletal muscle paralysis. The ubiquitous calcium sensor calmodulin (CaM) binds to an IQ motif in the C-terminal tail of the α-subunit of all NaV isoforms, and contributes to calcium-dependent pore-gating in some channels. Previous structural studies of calcium-free (apo) CaM bound to the IQ motifs of NaV1.2, NaV1.5, and NaV1.6 showed that CaM binding was mediated by the C-domain of CaM (CaMC), while the N-domain (CaMN) made no detectable contacts. To determine whether this domain-specific recognition mechanism is conserved in other NaV isoforms, we used solution NMR spectroscopy to assign the backbone resonances of complexes of apo CaM bound to peptides of IQ motifs of NaV1.1, NaV1.4, and NaV1.7. Analysis of chemical shift differences showed that peptide binding only perturbed resonances in CaMC; resonances of CaMN were identical to free CaM. Thus, CaMC residues contribute to the interface with the IQ motif, while CaMN is available to interact elsewhere on the channel.
Details
- Title: Subtitle
- Backbone resonance assignments of complexes of apo human calmodulin bound to IQ motif peptides of voltage-dependent sodium channels NaV1.1, NaV1.4 and NaV1.7
- Creators
- Holly Isbell - 0000 0004 1936 8294 grid.214572.7 Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City IA 52242-1109 USAAdina Kilpatrick - 0000 0001 0659 9139 grid.255228.a Department of Physics and Astronomy Drake University Des Moines IA 50311-4516 USAZesen Lin - 0000 0004 1936 8294 grid.214572.7 Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City IA 52242-1109 USARyan Mahling - 0000 0004 1936 8294 grid.214572.7 Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City IA 52242-1109 USAMadeline Shea - 0000 0004 1936 8294 grid.214572.7 Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine University of Iowa Iowa City IA 52242-1109 USA
- Resource Type
- Journal article
- Publication Details
- Biomolecular NMR assignments, Vol.12(2), pp.283-289
- DOI
- 10.1007/s12104-018-9824-5
- PMID
- 29728980
- PMCID
- PMC6274588
- NLM abbreviation
- Biomol NMR Assign
- ISSN
- 1874-2718
- eISSN
- 1874-270X
- Publisher
- Springer Netherlands; Dordrecht
- Grant note
- R01 GM57001; T32 NS045549 / National Institutes of Health (http://dx.doi.org/10.13039/100000002) Major Research Project / Office of the Vice President for Research and Economic Development, University of Iowa (http://dx.doi.org/10.13039/100011641) ICRU Fellowship / University of Iowa (http://dx.doi.org/10.13039/100008893) FUTURE in Biomedicine Program / Carver College of Medicine University of Iowa (US)
- Language
- English
- Date published
- 10/2018
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology
- Record Identifier
- 9984070221902771
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