Ion channels

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Template:STRUCTURE 1qrq

Ion channels are membrane proteins that catalyze the passive transport of ions through the cell membrane. Most ion channels are specific to an ion, like the sodium channels, or the chloride channels. Some, like the TRP channels, let through various cations. Another property of ion channels is that they can be either driven by voltage or concentration gradients, or they can be gated (by voltage, ligands, touch and other sensory signal). Potassium channels (KCh) are subdivided to voltage-gated KCh and calcium-dependent KCh. The latter are subdivided into high- (BK, LKCa), intermediate- and small-conductance KCh (human SK1, rat SK2, SKCa). MthK is a calcium-dependent potassium channel from Methanobacterium thermoautrophicum. MscL and MscS are large- and small-conductance mechanosensitive channels which protect bacteria from osmotic shock by allowing ions to flow across the cell membrane Mechanosensitive channels: opening and closing. Voltage-Dependent Calcium Channels (VDCC) allow Ca++ to enter the cell resulting in muscle contraction, neuron excitation or hormone release. VDCC are composed of several subunits and are named as a Cav gene product. Finally, ion channels are the fastest of all membrane transporters, with 106 to 108 transported units per second versus 102 to 104 molecules per second for porters/carriers, or 100 to 103 for ATP-driven pumps. The images at the left and at the right correspond to one representative ion channel structure, i.e. the crystal structure of voltage-dependent potassium channel from Rattus norvegicus (1qrq). Specific details in:

ClassificationClassification

TCDB, the most sophisticated classification of transport proteins to date, classify ion channels as a heterogenous subset of all α-type channels, whose singular property is to consist mainly of α-helices that span the membrane. They are distinct in this from the beta-barrel porins and the pore-forming toxins, as well as from non-ribosomally synthesized channels like gramicidin, polyglutamine or digitoxin. All these proteins are passive transport proteins.

Additional ResourcesAdditional Resources

For additional information, see: Membrane Channels & Pumps
For additional information, see: Hypertension & Congestive Heart Failure


Available 3D structuresAvailable 3D structures

Ion channels translate ionic fluxes across cell membrane into electrical impulses. MscL and MscS are large- and small-conductance mechanosensitive channels which protect bacteria from osmotic shock by allowing ions to flow across the cell membrane. Voltage-Dependent Calcium Channels (VDCC) allow Ca to enter the cell resulting in muscle contraction, neuron excitation or hormone release. VDCC are composed of several subunits and are named as a Cav gene product. The human annexin V molecule serves as a calcium channel. There are also Voltage-Dependent Anion Channels (VDAC). Chloride ion channels (ClCh) are involved in maintaining pH, volume homeostasis and more. Ligand-Gated Ion Channels (LGIC) open or close when binding a ligand like a neurotransmitter. The Cyclic Nucleotide-Gated channel (CNGC) conduct cations upon binding of cAMP or cGMP. The Acid-Sensitive channels (ASC) conduct cations upon binding of acid. The glycerol facilitator (GlpF) is a protein channel which transports glycerol across the cell membrane of E. coli. Other ion channel proteins are the aquaporins, gramicidin, antiamoebin, trichotoxin, peptaibol and the glutamate receptor.

Update February 2013

Potassium channelPotassium channel

See: Potassium Channels

Calcium channelCalcium channel

3bxx – rCav2.1 α 1A subunit+calmodulin
3bxl - rCav2.3 α 1E subunit+calmodulin
2f3y, 2f3z, 2be6 – hCav1.2 α 1C subunit+calmodulin
1t0h – rVDCC β 2A subunit
1t0j – rVDCC β 2A+α 1C
1vyt - rVDCC β 3+α 1C
1vyu – rVDCC β 3
1vyv - rVDCC β 4
1t3l - raVDCC β 2+α 1S – rabbit
1t3s - raVDCC β 2
2d46 – hVDCC β 4a – NMR
3dve, 3dvj, 3dvk, 3dvm, 3g43 - rCav2.2 α 1B subunit+hCalmodulin
3oxq - hCav2.1 α 1C subunit IQ domain+hCalmodulin
2vay, 3oxq - hCav1.1 α 1S subunit IQ domain+hCalmodulin
1hvd, 1hve, 1hvf, 1hvg – hAnnexin V (mutant)

Sodium channelSodium channel

1byy - rNaCh IIA inactivation fragment
2kav, 2kbi - hNaCh IIA C-terminal EF-hand domain - NMR

NH4+ channelNH4+ channel

2nmr, 2nop, 2now, 2npc, 2npd, 2npe, 2npj, 2npg, 2npk, 1u77, 1u7c, 1u7g, 1xqe, 1xqf – EcAmCh – Escherichia coli
2b2h, 2b2i, 2b2j, 2b2f – AmCh – Archaeglobus fulgidus
3b9w, 3b9y, 3bhs – AmCh – Nitrosomonas europaea

MscL and MscSMscL and MscS

3hzq – MscL – Staphylococcus aureus
2oar – MscL – Mycobacterium tuberculosis
2oau, 2vv5 - EcMscS

Chloride channelChloride channel

1rk4, 3swl - hClCh protein 1
3o3t, 3p8w, 3p90, 1k0o, 3qr6, 3tgz - hClCh protein 1 (mutant)
2per, 2r4v, 2r5g - hClCh protein 2
3kjy, 3fy7 - hClCh protein 3 residues 1-230
2ahe, 2d2z – hClCh protein 4

Anion ChannelAnion Channel

2jk4 – hVDAC

Ligand-gated ion channelLigand-gated ion channel

2vl0 – EcLGIC – Erwinia chrysanthemi
2yks - EcLGIC (mutant)
2xq3, 2xq4, 2xq5, 2xq6, 2xq7, 2xqa, 2xq8 – GvLGIC+inhibitor – Gloeobacter violaceus
3eam, 3ehz – GvLGIC
3igq – GvLGIC N-terminal
2xq9 – GvLGIC (mutant)+inhibitor
3p4w, 3p50 – GvLGIC + general anaesthetic
3lsv, 3tls, 3tlt, 3tlu, 3tlv, 3tlw, 3uu3, 3uu4, 3uu5, 3uu6, 3uu8, 3uub – GvLGIC (mutant)
4f8h – GvLGIC + ketamine
4a97, 4a98 – EcElic + benzodiazepine

Cyclic Nucleotide-Gated channelCyclic Nucleotide-Gated channel

3etq, 3ffq, 3u0z, 3u10, 3u11 - mCNGC C-terminal
1q3e, 1q43, 1q5o - mCNGC 2 fragment + nucleotide
2q0a - mCNGC 2 C-terminal (mutant)
3bpz - mCNGC 2 ligand-binding domain
2zd9, 3beh - MlCNGC
4chv, 4chw – MlCNGC – Cryo EM
2ptm - CNGC C-terminal - Strongylocentratus purpuratus
3co2 - MlCNGC ligand-binding domain (mutant) – Mesorhizobium loti
2kxl - ligand-binding domain – NMR
3beh - MlCNGC
3otf – hCNGC 4 ligand-binding domain
4hbn – hCNGC 4 ligand-binding domain (mutant)
4nvp – hCNGC 4 ligand-binding domain + 7-CH-cAMP

Acid sensitive ion channelAcid sensitive ion channel

3hgc, 3ij4, 2qts, 3s3w – cASC – chicken
3s3x, 4fz0, 4fz1 – cASC + psalmotoxin

ATP-Gated channel (AGC)ATP-Gated channel (AGC)

3h9v, 3i5d – AGC – Zebra fish

Proton channelProton channel

2kih, 2kwx – IVproton channel – Influenza virus
2rtf - IVproton channel + inhibitor - NMR
3c9j - IVproton channel transmembrane domain + inhibitor
3bkd - IVproton channel transmembrane domain
1nyj, 1mp6 - IVproton channel transmembrane domain - NMR
2kj1, 2l0j - IVproton channel – NMR

Voltage-gated hydrogen channel (VGHC)Voltage-gated hydrogen channel (VGHC)

3a2a – hVGHC C-terminal - NMR
3vmx – mVGHC C-terminal

Nicotinic acetylcholine receptorNicotinic acetylcholine receptor

1oed, 2bg9 - AChR - Torpeco marmorata - EM
2k58 - AChR β2 subunit 1st transmembrane domain - NMR
2k59 - AChR β2 subunit - NMR

Tryptophan channelTryptophan channel

2rfa - mTrpCh ankyrin repeat domain
3e7k - rTrpCh tetramerization domain

Glycerol facilitatorGlycerol facilitator

1lda, 1ldi - EcGlpF
1fx8 - EcGlpF + glycerol
1ldf - EcGlpF (mutant)

WeblinksWeblinks

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Ralf Stephan, Ilan Samish, Eric Martz, Wayne Decatur, Alexander Berchansky, Michal Harel, David Canner, Jaime Prilusky, Shelly Livne
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