Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Neurosci
2012 May 30;3222:7602-13. doi: 10.1523/JNEUROSCI.5727-11.2012.
Show Gene links
Show Anatomy links
The role of a voltage-dependent Ca2+ channel intracellular linker: a structure-function analysis.
Almagor L, Chomsky-Hecht O, Ben-Mocha A, Hendin-Barak D, Dascal N, Hirsch JA.
???displayArticle.abstract???
Voltage-dependent calcium channels (VDCCs) allow the passage of Ca(2+) ions through cellular membranes in response to membrane depolarization. The channel pore-forming subunit, α1, and a regulatory subunit (Ca(V)β) form a high affinity complex where Ca(V)β binds to a α1 interacting domain in the intracellular linker between α1 membrane domains I and II (I-II linker). We determined crystal structures of Ca(V)β2 functional core in complex with the Ca(V)1.2 and Ca(V)2.2 I-II linkers to a resolution of 1.95 and 2.0 Å, respectively. Structural differences between the highly conserved linkers, important for coupling Ca(V)β to the channel pore, guided mechanistic functional studies. Electrophysiological measurements point to the importance of differing linker structure in both Ca(V)1 and 2 subtypes with mutations affecting both voltage- and calcium-dependent inactivation and voltage dependence of activation. These linker effects persist in the absence of Ca(V)β, pointing to the intrinsic role of the linker in VDCC function and suggesting that I-II linker structure can serve as a brake during inactivation.
Abrahams,
Methods used in the structure determination of bovine mitochondrial F1 ATPase.
1996, Pubmed
Abrahams,
Methods used in the structure determination of bovine mitochondrial F1 ATPase.
1996,
Pubmed Arias,
Transfer of beta subunit regulation from high to low voltage-gated Ca2+ channels.
2005,
Pubmed Arias-Olguín,
Characterization of the gating brake in the I-II loop of Ca(v)3.2 T-type Ca(2+) channels.
2008,
Pubmed Baldwin,
Alpha-helix formation by peptides of defined sequence.
1995,
Pubmed Barrett,
The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.
2008,
Pubmed Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed Budde,
Calcium-dependent inactivation of neuronal calcium channels.
2002,
Pubmed Buraei,
The ß subunit of voltage-gated Ca2+ channels.
2010,
Pubmed Cens,
Voltage- and calcium-dependent inactivation in high voltage-gated Ca(2+) channels.
2006,
Pubmed
,
Xenbase Chen,
Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+ channels.
2004,
Pubmed Cowtan,
Density modification for macromolecular phase improvement.
1999,
Pubmed Creamer,
Alpha-helix-forming propensities in peptides and proteins.
1994,
Pubmed de La Fortelle,
[27] Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods.
1997,
Pubmed DeMaria,
Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels.
2001,
Pubmed De Waard,
Direct binding of G-protein betagamma complex to voltage-dependent calcium channels.
1997,
Pubmed
,
Xenbase Emsley,
Coot: model-building tools for molecular graphics.
2004,
Pubmed Findeisen,
Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation.
2009,
Pubmed
,
Xenbase Fox,
Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones.
1987,
Pubmed Gonzalez-Gutierrez,
Swapping the I-II intracellular linker between L-type CaV1.2 and R-type CaV2.3 high-voltage gated calcium channels exchanges activation attributes.
2010,
Pubmed
,
Xenbase Greenfield,
Conformational intermediates in the folding of a coiled-coil model peptide of the N-terminus of tropomyosin and alpha alpha-tropomyosin.
1993,
Pubmed Haebel,
Crystallization and initial crystallographic analysis of the disulfide bond isomerase DsbC in complex with the alpha domain of the electron transporter DsbD.
2001,
Pubmed Hamada,
High helical propensity of the peptide fragments derived from beta-lactoglobulin, a predominantly beta-sheet protein.
1995,
Pubmed He,
Functional modularity of the beta-subunit of voltage-gated Ca2+ channels.
2007,
Pubmed Hoshi,
Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.
1991,
Pubmed
,
Xenbase Jones,
Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology.
1989,
Pubmed Jones,
Overview of voltage-dependent calcium channels.
1998,
Pubmed Kang,
Biochemical and biophysical evidence for gamma 2 subunit association with neuronal voltage-activated Ca2+ channels.
2001,
Pubmed
,
Xenbase Kim,
Identification of the components controlling inactivation of voltage-gated Ca2+ channels.
2004,
Pubmed
,
Xenbase Lee,
Ca2+/calmodulin-dependent facilitation and inactivation of P/Q-type Ca2+ channels.
2000,
Pubmed Lee,
Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.
1999,
Pubmed Lee,
Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium.
1985,
Pubmed Liang,
Unified mechanisms of Ca2+ regulation across the Ca2+ channel family.
2003,
Pubmed López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase Meuth,
Modulation of Ca2+ currents in rat thalamocortical relay neurons by activity and phosphorylation.
2002,
Pubmed Mori,
Functional stoichiometry and local enrichment of calmodulin interacting with Ca2+ channels.
2004,
Pubmed Müller,
Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain.
2010,
Pubmed Muñoz,
Development of the multiple sequence approximation within the AGADIR model of alpha-helix formation: comparison with Zimm-Bragg and Lifson-Roig formalisms.
1997,
Pubmed Murshudov,
Refinement of macromolecular structures by the maximum-likelihood method.
1997,
Pubmed O'Neil,
A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids.
1990,
Pubmed Opatowsky,
The voltage-dependent calcium channel beta subunit contains two stable interacting domains.
2003,
Pubmed
,
Xenbase Opatowsky,
Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain.
2004,
Pubmed Otwinowski,
Processing of X-ray diffraction data collected in oscillation mode.
1997,
Pubmed Pace,
A helix propensity scale based on experimental studies of peptides and proteins.
1998,
Pubmed Patil,
Preferential closed-state inactivation of neuronal calcium channels.
1998,
Pubmed Perrakis,
Automated protein model building combined with iterative structure refinement.
1999,
Pubmed Peterson,
Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels.
1999,
Pubmed Peterson,
Critical determinants of Ca(2+)-dependent inactivation within an EF-hand motif of L-type Ca(2+) channels.
2000,
Pubmed Pragnell,
Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit.
1994,
Pubmed Richmond,
Slow inactivation in human cardiac sodium channels.
1998,
Pubmed
,
Xenbase Shistik,
Crucial role of N terminus in function of cardiac L-type Ca2+ channel and its modulation by protein kinase C.
1998,
Pubmed
,
Xenbase Spaetgens,
Multiple structural domains contribute to voltage-dependent inactivation of rat brain alpha(1E) calcium channels.
1999,
Pubmed Tareilus,
A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit.
1997,
Pubmed
,
Xenbase Tselnicker,
Stargazin modulates neuronal voltage-dependent Ca(2+) channel Ca(v)2.2 by a Gbetagamma-dependent mechanism.
2010,
Pubmed
,
Xenbase Van Petegem,
Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.
2004,
Pubmed Vilin,
Structural determinants of slow inactivation in human cardiac and skeletal muscle sodium channels.
1999,
Pubmed
,
Xenbase Vitko,
Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity.
2008,
Pubmed Wakamori,
Auxiliary subunits operate as a molecular switch in determining gating behaviour of the unitary N-type Ca2+ channel current in Xenopus oocytes.
1999,
Pubmed
,
Xenbase Wakamori,
Functional characterization of ion permeation pathway in the N-type Ca2+ channel.
1998,
Pubmed Waterhouse,
Jalview Version 2--a multiple sequence alignment editor and analysis workbench.
2009,
Pubmed Zhang,
Origin of the voltage dependence of G-protein regulation of P/Q-type Ca2+ channels.
2008,
Pubmed
,
Xenbase Zühlke,
Ca2+-sensitive inactivation of L-type Ca2+ channels depends on multiple cytoplasmic amino acid sequences of the alpha1C subunit.
1998,
Pubmed
,
Xenbase
