ArticleProceedings of the National Academy of Sciences of the United States of America2008
The guanylate kinase domain of the beta-subunit of voltage-gated calcium channels suffices to modulate gating.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Mapping the interaction surface between CaNature communications · 2025Article
- Nanoenviroments of the β-Subunit of L-Type Voltage-Gated Calcium Channels in Adult Cardiomyocytes.Frontiers in cell and developmental biology · 2021Article
- Direct interaction of CaVβ with actin up-regulates L-type calcium currents in HL-1 cardiomyocytes.The Journal of biological chemistry · 2015Article
- The N-terminal domain tethers the voltage-gated calcium channel β2e-subunit to the plasma membrane via electrostatic and hydrophobic interactions.The Journal of biological chemistry · 2014Article
- Structure-function of proteins interacting with the α1 pore-forming subunit of high-voltage-activated calcium channels.Frontiers in physiology · 2014Review
- Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism.Nature genetics · 2013Article
- Structure and function of the β subunit of voltage-gated Ca²⁺ channels.Biochimica et biophysica acta · 2013Review
- A short polybasic segment between the two conserved domains of the β2a-subunit modulates the rate of inactivation of R-type calcium channel.The Journal of biological chemistry · 2012Article
- A quartet of leucine residues in the guanylate kinase domain of CaVβ determines the plasma membrane density of the CaV2.3 channel.The Journal of biological chemistry · 2012Article
- Enzyme closure and nucleotide binding structurally lock guanylate kinase.Biophysical journal · 2011Article
- Homodimerization of the Src homology 3 domain of the calcium channel β-subunit drives dynamin-dependent endocytosis.The Journal of biological chemistry · 2011Article
- Gαi2- and Gαi3-specific regulation of voltage-dependent L-type calcium channels in cardiomyocytes.PloS one · 2011Article
- Oligomerization of Cavbeta subunits is an essential correlate of Ca2+ channel activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- The ß subunit of voltage-gated Ca2+ channels.Physiological reviews · 2010Review
- Ahnak1 modulates L-type Ca(2+) channel inactivation of rodent cardiomyocytes.Pflugers Archiv : European journal of physiology · 2010Article
- The voltage-gated calcium-channel beta subunit: more than just an accessory.European biophysics journal : EBJ · 2009Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inactivation of voltage-gated calcium channels is crucial for the spatiotemporal coordination of calcium signals and prevention of toxic calcium buildup. Only one member of the highly conserved family of calcium channel beta-subunits--Ca(V)beta--inhibits inactivation. This unique property has been attributed to short variable regions of the protein; however, here we report that this inhibition actually is conferred by a conserved guanylate kinase (GK) domain and, moreover, that this domain alone recapitulates Ca(V)beta-mediated modulation of channel activation. We expressed and refolded the GK domain of Ca(V)beta(2a), the unique variant that inhibits inactivation, and of Ca(V)beta(1b), an isoform that facilitates it. The refolded domains of both Ca(V)beta variants were found to inhibit inactivation of Ca(V)2.3 channels expressed in Xenopus laevis oocytes. These findings suggest that the GK domain endows calcium channels with a brake restraining voltage-dependent inactivation, and thus facilitation of inactivation by full-length Ca(V)beta requires additional structural determinants to antagonize the GK effect. We found that Ca(V)beta can switch the inactivation phenotype conferred to Ca(V)2.3 from slow to fast after posttranslational modifications during channel biogenesis. Our findings provide a framework within which to understand the modulation of inactivation and a new functional map of Ca(V)beta in which the GK domain regulates channel gating and the other conserved domain (Src homology 3) may couple calcium channels to other signaling pathways.
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