Ion channels

File:1qrq1.png

Crystal structure of voltage-dependent potassium channel, 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. 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).

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 structuresAvailable structures

Membrane transport proteins are notoriously difficult to crystallize while in a working state. So, it's no surprise that there are preciously few structure data for ion channels. At the moment, the following α-type ion channels have been at least partly resolved:

• the voltage-dependent potassium channel K₁ from Rattus norvegicus (1qrq, 1exb, 1t1d, 2a79, 2r9r, 3eau, 3eb3, 3eb4)
• the voltage-dependent calcium channel from Rattus norvegicus (L-type: 1t0h, 1t0j, 1vyt, 1vyu, 1vyv, 2vay, 3bxk, R-type: 3bxl)
• the voltage-gated potassium channel KcsA from Streptomyces lividans and Mus musculus with the structures 1bl8, 1k4c, 1jq2, 1k4d, 2bob, 2boc, 2hg5,2h8p, 2hfe, 2itc, 2itd, 2k1e, 2nlj
• the voltage-gated potassium channel K_AP from Aeropyrum pernix (1orq, 2a0l), and human K₇ (2ovc, 3bj4)
• the voltage-gated sodium channel Na_1.2 (1byy, 2kav) and Na_1.5 (2kbi)
• the ligand-gated ion channel that is the glutamate receptor from Rattus norvegicus (3kg2)
• the calcium-gated potassium channel mthK from Methanobacterium thermoautotrophicum (1lnq, 2fy8)
• the hyperpolarization-activated and cyclic nucleotide-gated K+ channel HCN from Mus musculus (1q3e, 1q43, 1q5o, 2ptm, 2q0a, 3bpz)
• the inward rectifier potassium channels KirBac3.1 (1xl4,1xl6) and Kir3.1 (Cyt. only: 1n9p, 1u4e, 1u4f, 1p7b, 2e4f)
• the acid-sensitive (proton-gated) cation channel ASIC from Gallus gallus (2qts)
• the human intracellular chloride channel CLIC-2 (2per, 2r4v, 2r5g)
• the nicotinic acetylcholine-activated cation-selective channel from Torpedo marmorata (1oed, 2bg9, 2k58, 2k59)
• a potassium channel from Burkholderia pseudomallei (1p7b)
• the ammonium transporter from Archaeoglobus fulgidus (2b2f) and from Nitrosomonas europaea (3b9y, 3b9z, 3bhs)
• the small-conductance mechanosensitive channel from E. coli K12 (2oau, 2vv5, see also 2k2b)
• TRP channels (2rfa, 3e7k)
• human phospholamban (1zll, 2hyn)
• the P7 viroporin of Hepatitis C virus (2k8j)
• the M2 proton channel from Influenza A (3bkd, 1nyj, 2kad, 2rlf, 3c9j)
  • featured in a morph at Proton Channels.
• aquaporins from several species:
  • Methanobacterium thermoautotrophicum (aqpM, 2evu, 2f2c)
  • E. coli K12 (Aquaporin Z, 1r2c, 2abm)
  • the glycerol uptake facilitator from E. coli K12 (GlpF, 1lda, 1ldf, 1ldi, 1fx8)
  • Homo sapiens (AQP-1, 1fqy, 1ih5)
  • Bos taurus (Aquaporin-0, 1ymg, 2b6p)

Calcium-dependent potassium channels from Methanobacterium thermoautrophicum (MthK):

• 1kxd – MthK RCK domain+Cd - Methanobacterium thermoautrophicum
• 2ogu, 2fy8, 2aej, 2aem, 1lnq - MthK RCK domain
• 2aef - MthK RCK domain+Ca

Large- and small-conductance mechanosensitive channels (MscL and MscS):

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

Additionally the following non-ribosomally synthesized channel proteins constitute ion channels, and have their structure resolved:

• Gramicidin (1av2, 1c4d, 1mag)
  • See also the theoretical model of a gramicidin channel in a hydrated lipid bilayer.
• fungal Antiamoebin (1joh, 1gq0)
• fungal Trichotoxin (1m24)
• further Peptaibol antibiotics (1ob4, 1ob6, 1ob7)

We do not count ClC chloride carriers as ion channels, as they are secondary active carriers.

Available 3D structuresAvailable 3D structures

Ion channels translate ionic fluxes across cell membrane into electrical impulses. 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. 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.

Potassium channelPotassium channel

See: Potassium Channels

BK channelBK channel

3mt5 – hBK cytoplasmic domain
1jo6 – BK beta 2 N- terminal KCNMB2 encoded LKCa - NMR

MthKMthK

1kxd – MthK RCK domain+Cd - Methanobacterium thermoautrophicum
2ogu, 2fy8, 2aej, 2aem, 1lnq - MthK RCK domain
2aef - MthK RCK domain+Ca

Calcium channelCalcium channel

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

NH4+ channelNH4+ channel

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

MscL and MscSMscL and MscS

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

Chloride channelChloride channel

2ahe, 2d2z – hClCh protein 4
1rk4 - hClCh protein 1
3o3t, 3p8w, 3p90, 1k0o - hClCh protein 1 (mutant)

Anion ChannelAnion Channel

2jk4 – hVDAC

Ligand-gated ion channelLigand-gated ion channel

2vl0 – LGIC – Erwinia chrysanthemi
2xq3, 2xq4, 2xq5, 2xq6, 2xq7, 2xqa, 2xq8 – GvLGIC+inhibitor – Gloeobacter violaceus
3eam, 3ehz – GvLGIC
3igq – GvLGIC N-terminal
2xq9 – GvLGIC (mutant)+inhibitor
3lsv – GvLGIC (mutant)

Cyclic Nucleotide-Gated channelCyclic Nucleotide-Gated channel

3etq, 3ffq – mCNGC C-terminal
2zd9, 3beh - MlCNGC

Acid sensitive ion channelAcid sensitive ion channel

3hgc, 3ij4 – ASC – chicken

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

3h9v, 3i5d – AGC – Zebra fish

Proton channelProton channel

2kih, 2kwx – IVproton channel – Influenza virus
2kj1, 2l0j - IVproton channel – NMR

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

3a2a – hVGHC C-terminal - NMR

WeblinksWeblinks

• The TCDB database
• TCDB: 1.A α-Type channels
• TCDB: Transport proteins with PDB structures