User:Amy Kerzmann/Sandbox 4
From Proteopedia
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| - | == | + | == Voltage-Gated Calcium Channels == |
| + | <applet load='1t0j' size='300' frame='true' align='left' | ||
| + | caption='VOLTAGE-GATED CALCIUM CHANNNEL' /> | ||
| - | + | Voltage-gated calcium channels play crucial roles in many bodily functions | |
| - | + | including: cardiac action potentials, neurotransmitter release, muscle | |
| + | contraction. During neurological functions, these calcium channels create | ||
| + | action potentials. At resting state,voltage-gated calcium channels are in a | ||
| + | closed conformation. When the membrane is depolarized, they are open. The | ||
| + | pore-forming α1-subunit of voltage-gated Ca2+ channels (Cav)2 is composed of | ||
| + | four homologous domains (I-IV), each of which has six transmembrane segments | ||
| + | (S1–S6). These channels initiate the release of neurotransmitters at | ||
| + | synapses, and have a powerful influence on synaptic strength. The nervous | ||
| + | system requires different levels of calcium concentration, so when | ||
| + | transmitter release occurs, high levels of calcium are needed. During | ||
| + | short-term facilitation, slow steady streams of calcium build up. Failure | ||
| + | of these calcium channels can result in migranes, ataxia, and also other | ||
| + | neurological diseases. Calmodulin is a specific calcium channel sensor, and | ||
| + | regulates the functions of the channel. Calcium binding to calmodulin | ||
| + | regulates the facilitation of Ca2+ through the coltage-gated channels. | ||
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| - | + | == Structure == | |
| - | + | This specific protein is a two chain structure and was first found in Rattus | |
| - | + | norvegicus. | |
| - | + | ||
| - | + | The beta-interaction domain (BID), formed the AID-binding site; however, | |
| + | this region is buried in the Ca(V)beta core and is unavailable for | ||
| + | protein-protein interactions. | ||
| - | Purified CLIC1 can integrate into synthetic lipid bilayers forming a | ||
| - | chloride channel with similar properties to those observed in vivo. The | ||
| - | structure of the soluble form of CLIC1 has been determined at 1.4-A | ||
| - | resolution, and is shown to the right. It's a homodimeric structure with one | ||
| - | pore per subunit, creating a "double barreled" channel. At its binding site | ||
| - | in the pore, chloride interacts with the ends of four helices that come from | ||
| - | both sides of the membrane. A <scene | ||
| - | name='User:Laura_Fountain/Sandbox_1/Glutamate_residue/1'>glutamate | ||
| - | residue</scene> that protrudes into the pore is proposed to participate in | ||
| - | gating.<ref>PMID:#12163078</ref> Integration of CLIC1 into the membrane is | ||
| - | likely to require a major structural rearrangement, probably of the N-domain | ||
| - | (<scene name='User:Laura_Fountain/Sandbox_1/N-domain/3'>residues | ||
| - | 1-90</scene>), with the putative transmembrane helix arising from residues | ||
| - | in the vicinity of the redox-active site.<ref>PMID:#11551966</ref> | ||
| - | While this exact mechanism isn't known, it has been shown that functionality | ||
| - | of the channel doesn't change whether it goes through 'normal' membrane | ||
| - | integration via vesicles, or whether it's inserted into the intracellular | ||
| - | space and allowed to integrate itself.<ref>PMID:#11940526</ref> Littler et. | ||
| - | al. propose that upon oxidation CLIC1 undergoes a reversible transition from | ||
| - | a monomeric to a non-covalent dimeric state due to the formation of an | ||
| - | intramolecular disulfide bond (<scene | ||
| - | name='User:Laura_Fountain/Sandbox_1/Cys_visualization/1'>Cys-24-Cys-59</scen | ||
| - | e>). They have determined the crystal structure of this oxidized state and | ||
| - | show that a major structural transition has occurred, exposing a large | ||
| - | hydrophobic surface, which forms the dimer interface. The oxidized CLIC1 | ||
| - | dimer maintains its ability to form chloride ion channels in artificial | ||
| - | bilayers and vesicles, whereas a reducing environment prevents the formation | ||
| - | of ion channels by CLIC1. Their mutational studies show that both Cys-24 and | ||
| - | Cys-59 are required for channel activity.<ref>PMID:#14613939</ref> | ||
| - | 1K0O is a 2 chains structure of sequences from Homo sapiens. The protein is | ||
| - | monomeric and structurally homologous to the glutathione S-transferase | ||
| - | superfamily, and it has a redox-active site resembling glutaredoxin. The | ||
| - | structure of the complex of CLIC1 with glutathione shows that glutathione | ||
| - | occupies the redox-active site, which is adjacent to an open, elongated slot | ||
| - | lined by basic residues. This structure indicates that CLIC1 is likely to be | ||
| - | controlled by redox-dependent processes.<ref>PMID:#11551966</ref> | ||
| - | == References == | ||
| - | < | + | |
| + | |||
| + | ---- | ||
| + | [http://www.ncbi.nlm.nih.gov/pubmed/17052221] | ||
| + | [[http://www.ncbi.nlm.nih.gov/pubmed/18817729?ordinalpos=1=EntrezSyste <http://www.ncbi.nlm.nih.gov/pubmed/18817729?ordinalpos=1&itool=EntrezSyste> | ||
| + | m2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_Title | ||
| + | Search&linkpos=1&log$=pmtitlesearch4]] | ||
| + | [[http://www.ncbi.nlm.nih.gov/pubmed/18817727?ordinalpos=1=EntrezSyste <http://www.ncbi.nlm.nih.gov/pubmed/18817727?ordinalpos=1&itool=EntrezSyste> | ||
| + | m2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery | ||
| + | _RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed]] | ||
| + | [[http://www.jbc.org/content/282/6/3864.full]] | ||
| + | [[Catterall, W. A., Perez-Reyes, E., Snutch, T. P., and Striessnig, J. | ||
| + | (2005) Pharmacol. Rev. 57, 411-425Abstract/FREE Full Text]] | ||
| + | [http://www.ncbi.nlm.nih.gov/pubmed/16369047?ordinalpos=1=EntrezSystem <http://www.ncbi.nlm.nih.gov/pubmed/16369047?ordinalpos=1&itool=EntrezSystem> | ||
| + | 2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_ | ||
| + | RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed] | ||
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| + | <scene name='User:Kyle_Barrett/Voltage-gated_calcium_channel/1'>Polarity | ||
| + | model of voltage-gated calcium channel</scene> | ||
Revision as of 01:05, 6 October 2009
Voltage-Gated Calcium Channels
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Voltage-gated calcium channels play crucial roles in many bodily functions including: cardiac action potentials, neurotransmitter release, muscle contraction. During neurological functions, these calcium channels create action potentials. At resting state,voltage-gated calcium channels are in a closed conformation. When the membrane is depolarized, they are open. The pore-forming α1-subunit of voltage-gated Ca2+ channels (Cav)2 is composed of four homologous domains (I-IV), each of which has six transmembrane segments (S1–S6). These channels initiate the release of neurotransmitters at synapses, and have a powerful influence on synaptic strength. The nervous system requires different levels of calcium concentration, so when transmitter release occurs, high levels of calcium are needed. During short-term facilitation, slow steady streams of calcium build up. Failure of these calcium channels can result in migranes, ataxia, and also other neurological diseases. Calmodulin is a specific calcium channel sensor, and regulates the functions of the channel. Calcium binding to calmodulin regulates the facilitation of Ca2+ through the coltage-gated channels.
Structure
This specific protein is a two chain structure and was first found in Rattus norvegicus.
The beta-interaction domain (BID), formed the AID-binding site; however, this region is buried in the Ca(V)beta core and is unavailable for protein-protein interactions.
[1] [[http://www.ncbi.nlm.nih.gov/pubmed/18817729?ordinalpos=1=EntrezSyste <http://www.ncbi.nlm.nih.gov/pubmed/18817729?ordinalpos=1&itool=EntrezSyste> m2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_Title Search&linkpos=1&log$=pmtitlesearch4]] [[http://www.ncbi.nlm.nih.gov/pubmed/18817727?ordinalpos=1=EntrezSyste <http://www.ncbi.nlm.nih.gov/pubmed/18817727?ordinalpos=1&itool=EntrezSyste> m2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery _RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed]] [[2]] [[Catterall, W. A., Perez-Reyes, E., Snutch, T. P., and Striessnig, J. (2005) Pharmacol. Rev. 57, 411-425Abstract/FREE Full Text]] [http://www.ncbi.nlm.nih.gov/pubmed/16369047?ordinalpos=1=EntrezSystem <http://www.ncbi.nlm.nih.gov/pubmed/16369047?ordinalpos=1&itool=EntrezSystem> 2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_ RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed]
