Repositioning of charged I-II loop amino acid residues within the electric field by beta subunit as a novel working hypothesis for the control of fast P/Q calcium channel inactivation

Previous studies have shown that NH2 termini of the type 1 and 2 beta-subunits modulate the rate at which the neuronal alpha 1E calcium channel inactivates in response to voltage and that they do so independently of their common effect to stimulate activation by voltage (R. Olcese, N. Qin, T. Schneider, A. Neely, X. Wei, E. Stefani, and L. Birnbaumer, Neuron 13: 1433-1438, 1994). By constructing NH2-terminal deletions of several splice variants of beta-subunits, we have now found differences in the way they affect the rate of alpha 1E inactivation that lead us to identify a second domain that also regulates the rate of voltage-induced inactivation of the Ca2+ channel. This second domain, named segment 3, lies between two regions of high-sequence identity between all known beta-subunits and exists in two lengths (long and short), each encoded in a separate exon. Beta-Subunits with the longer 45- to 53-amino acid version cause the channel to inactivate more slowly than subunits with the shorter 7-amino acid version. As is the case for the NH2 terminus, the segment 3 does not affect the regulation of channel activation by the beta-subunit. In addition, the effect of the NH2-terminal segment prevails over that of the internal segment. This raises the possibility that phosphorylation, other types of posttranslational modification, or interaction with other auxiliary calcium channel subunits may be necessary to unmask the regulatory effect of the internal segment.

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Identification of conserved amino acid residues in the beta subunit of human choriogonadotropin important in holoprotein formation.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)32401-8 ◽

1994 ◽

Vol 269 (27) ◽

pp. 17944-17953

Author(s):

H. Xia ◽

D. Puett

Keyword(s):

Amino Acid ◽

Beta Subunit ◽

Amino Acid Residues ◽

Human Choriogonadotropin

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Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator

Marine Drugs ◽

10.3390/md18070343 ◽

2020 ◽

Vol 18 (7) ◽

pp. 343

Author(s):

Dan Wang ◽

S.W.A. Himaya ◽

Jean Giacomotto ◽

Md. Mahadhi Hasan ◽

Fernanda C. Cardoso ◽

...

Keyword(s):

Amino Acid ◽

Ion Channel ◽

Calcium Channel ◽

Binding Sites ◽

Molluscan Neurons ◽

Cone Snail ◽

Voltage Gated ◽

Channel Inactivation ◽

High Concentrations ◽

Channel Modulator

The 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail Conus textile, slows voltage-gated sodium (NaV) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian NaV1.2 and NaV1.7 even at high concentrations (10 µM). Given the fact that invertebrate NaV channel and T-type calcium channels (CaV3.x) are evolutionarily related, we examined the possibility that TxVIA may act on CaV3.x. Electrophysiological characterisation of the native TxVIA on CaV3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits CaV3.2 current (IC50 = 0.24 μM) and enhances CaV3.1 current at higher concentrations. In fish bioassays TxVIA showed little effect on zebrafish behaviours when injected intramuscular at 250 ng/100 mg fish. The binding sites for TxVIA at NaV1.7 and CaV3.1 revealed that their channel binding sites contained a common epitope.

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Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation

The Journal of General Physiology ◽

10.1085/jgp.200810143011310c ◽

2010 ◽

Vol 135 (2) ◽

pp. 169-169

Author(s):

Felix Findeisen ◽

Daniel L. Minor

Keyword(s):

Calcium Channel ◽

Voltage Gated ◽

Channel Inactivation ◽

Calcium Channel Inactivation ◽

Voltage Gated Calcium Channel

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Identification of amino acid residues photolabeled with 2-azido[.alpha.-32P]adenosine diphosphate in the .beta. subunit of beef heart mitochondrial F1-ATPase

Biochemistry ◽

10.1021/bi00363a039 ◽

1986 ◽

Vol 25 (15) ◽

pp. 4431-4437 ◽

Cited By ~ 87

Author(s):

Jerome Garin ◽

Francois Boulay ◽

Jean Paul Issartel ◽

Joel Lunardi ◽

Pierre V. Vignais

Keyword(s):

Amino Acid ◽

Adenosine Diphosphate ◽

Beta Subunit ◽

Beef Heart ◽

Amino Acid Residues ◽

F1 Atpase

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The genomic basis of electrotaxis in Dictyostelium discoideum: Electric field sensitive amino acids are dynamically encoded en masse for the streaming-stage proteome

10.1101/034892 ◽

2015 ◽

Author(s):

Albert J Erives

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Electric Field ◽

Electric Fields ◽

Large Scale ◽

Genetic Model ◽

Critical Role ◽

Axon Growth ◽

Amino Acid Residues ◽

Signaling Systems

Electrotaxis plays a critical role in developmental cell migration, axon growth cone guidance, epithelial wound healing, tissue regeneration, and the degree of invasiveness characterizing different cancer cell lines. During electrotaxis in a direct current electric field (EF), a cell migrates preferentially either towards the anode or cathode depending on the cell-type. However, the types and ranges of mechanisms coupling trans-cellular electric fields to cellular EF-sensitive signaling systems are largely unknown. To address this cell biological phenomenon, I use transcriptomic data from a developmental genetic model in which multicellular social aggregation is induced by starvation of amoeboid cells. I find that the developmental proteome expressed during the streaming aggregation stage is measurably and substantially enriched in charged and highly polar amino acids relative to the proteomes of either the unicellular amoeboid or the multicellular fruiting body. This large-scale coding augmentation of EF-sensitive amino acid residues in thousands of streaming-specific proteins is accompanied by a proportional coding decrease in the number of small, uncharged amino acid residues. I also confirm an expected coding increase of biosynthetically costly amino acids in the proteome of the satiated feeding-stage amoeboid. These findings suggest that electrotactic capability is encoded broadly in the genetically regulated deployment of a developmental proteome with augmented EF-sensitivity. These results signify that extreme, nonuniform, evolutionary constraints can be exerted on the amino acid composition of an organism’s proteome.

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