3OXQ

Crystal Structure of Ca2+/CaM-CaV1.2 pre-IQ/IQ domain complex

Summary for 3OXQ

• Entry DOI: 10.2210/pdb3oxq/pdb
• Descriptor: Calmodulin, Voltage-dependent L-type calcium channel subunit alpha-1C, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: ef hand iq domain, calcium sensing, calcium binding, ion channel, 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: 6
• Total formula weight: 86234.65

Authors

Kim, E.Y.,Rumpf, C.H.,Van Petegem, F.,Arant, R.,Findeisen, F.,Cooley, E.S.,Isacoff, E.Y.,Minor, D.L. (deposition date: 2010-09-21, release date: 2010-11-03, Last modification date: 2023-09-06)

Primary citation

Kim, E.Y.,Rumpf, C.H.,Van Petegem, F.,Arant, R.J.,Findeisen, F.,Cooley, E.S.,Isacoff, E.Y.,Minor, D.L.
Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.
Embo J., 29:3924-3938, 2010

PubMed Abstract: Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site.

PubMed: 20953164
DOI: 10.1038/emboj.2010.260

Experimental method

X-RAY DIFFRACTION (2.55 Å)