2LQC

NMR solution structure of a Ca2+-Calmodulin with a binding motif (NSCaTE) peptide from the N-terminal cytoplasmic domain of the L-type Voltage-Cated Calcium Channel alpha1C subunit

Summary for 2LQC

• Entry DOI: 10.2210/pdb2lqc/pdb
• NMR Information: BMRB: 18302
• Descriptor: Calmodulin, Voltage-dependent L-type calcium channel subunit alpha-1C, CALCIUM ION (3 entities in total)
• Functional Keywords: metal binding protein-transport protein complex, metal binding protein/transport protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62158; Membrane; Multi-pass membrane protein: Q13936
• Total number of polymer chains: 2
• Total formula weight: 11011.34

Authors

Liu, Z. (deposition date: 2012-02-29, release date: 2012-06-06, Last modification date: 2024-05-01)

Primary citation

Liu, Z.,Vogel, H.J.
Structural basis for the regulation of L-type voltage-gated calcium channels: interactions between the N-terminal cytoplasmic domain and Ca(2+)-calmodulin.
Front Mol Neurosci, 5:38-38, 2012

PubMed Abstract: It is well-known that the opening of L-type voltage-gated calcium channels can be regulated by calmodulin (CaM). One of the main regulatory mechanisms is calcium-dependent inactivation (CDI), where binding of apo-CaM to the cytoplasmic C-terminal domain of the channel can effectively sense an increase in the local calcium ion concentration. Calcium-bound CaM can bind to the IQ-motif region of the C-terminal region and block the calcium channel, thereby providing a negative feedback mechanism that prevents the rise of cellular calcium concentrations over physiological limits. Recently, an additional Ca(2+)/CaM-binding motif (NSCaTE, N-terminal spatial Ca(2+) transforming element) was identified in the amino terminal cytoplasmic region of Ca(v)1.2 and Ca(v)1.3. This motif exists only in Ca(v)1.2 and Ca(v)1.3 channels, and a pronounced N-lobe (Ca(2+)/CaM) CDI effect was found for Ca(v)1.3. To understand the molecular basis of this interaction, the complexes of Ca(2+)/CaM with the biosynthetically produced N-terminal region (residues 1-68) and NSCaTE peptide (residues 48-68) were investigated. We discovered that the NSCaTE motif in the N-terminal cytoplasmic region adopts an α-helical conformation, most likely due to its high alanine content. Additionally, the complex exhibits an unusual 1:2 protein:peptide stoichiometry when bound to Ca(2+)-CaM, and the N-lobe of CaM has a much stronger affinity for the peptide than the C-lobe. The complex structures of the isolated N- and C-lobe of Ca(2+)/CaM and the NSCaTE peptide were determined by nuclear magnetic resonance spectroscopy and data-driven protein-docking methods. Moreover, we also demonstrated that calcium binding protein 1, which competes with CaM for binding to the C-terminal cytoplasmic domain, binds only weakly to the NSCaTE region. The structures provide insights into the possible roles of this motif in the calcium regulatory network. Our study provides structural evidence for the CaM-bridge model proposed in previous studies.

PubMed: 22518098
DOI: 10.3389/fnmol.2012.00038

Experimental method

SOLUTION NMR