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694  structures 5912  species 0  interactions 38525  sequences 524  architectures

Family: Ion_trans_2 (PF07885)

Summary: Ion channel

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Cation channel superfamily". More...

Cation channel superfamily Edit Wikipedia article

Ion transport protein
Identifiers
SymbolIon_trans
PfamPF00520
InterProIPR005821
SCOP21bl8 / SCOPe / SUPFAM
TCDB1.A.1
OPM superfamily8
OPM protein2a79


Ion channel
Identifiers
SymbolIon_trans_2
PfamPF07885
InterProIPR013099
SCOP21bl8 / SCOPe / SUPFAM
OPM protein2a0l


Transmembrane ion channel family, as defined in InterPro and Pfam, consists of tetrameric sodium, potassium, and calcium ion channels, in which two C-terminal transmembrane helices flank a loop which determines ion selectivity of the channel pore. This apparently corresponds to 1.A.1 1.A.2 1.A.3 and 1.A.4 families.


Many eukariotic channels have four additional transmembrane helices (Template:Pfam= PF00520), wheras a bacterial structure of the protein has only two central transmembrane helices lacking the first four helices(Pfam PF07885

In some sub-families (e.g. Na channels) the six-helical domain is repeated four times, whereas in others (e.g. K channels) the protein exists as a tetramer in the membrane.

Human proteins containing 6-helical domain


Human proteins containing two-helical domain found in bacteria

References

  • [1]. Potassium channel structures. Choe S; Nat Rev Neurosci 2002;3:115-121. PMID 11836519


This article incorporates text from the public domain Pfam and InterPro: IPR005821

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Ion channel family". More...

Ion channel family Edit Wikipedia article

  • From a page move: This is a redirect from a page that has been moved (renamed). This page was kept as a redirect to avoid breaking links, both internal and external, that may have been made to the old page name.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "KcsA potassium channel". More...

KcsA potassium channel Edit Wikipedia article

A KcsA potassium channel is a prokaryotic potassium ion channel from the soil bacteria Streptomyces Lividans activated by changes in pH [1]. Roderick MacKinnon and his colleagues were the first to crystallize a KcsA potassium channel.
KcsA has become the most extensively studied potassium channel, and is widely used as the template in potassium channel research [2].

KcsA Channel Topology

KcsA is a tetramer composed of four identical subunits of two transmembrane helices (the outer-helix M1 and the inner-helix M2) linked by a reentrant loop, dispersed symmetrically around a common axis corresponding to the central pore. The pore can be divided into three parts: a selectivity filter near the extracellular side, a dilated water-filled cavity at the center, and a closed gate near the cytoplasmic side formed by four packed M2 helices. This architecture is found to be highly conserved in the potassium channel family [3] [4], including both the eukaryotic and prokaryotic ones.

The KcsA channel is a proton-activated potassium channel that opens at acidic pH [5] [6]. The KcsA channel has two pH-sensing regions: 1) the charge cluster region at the boundary between the membrane and cytoplasm, and 2) the cytoplasmic domain. There is evidence to suggest that the main pH sensor is in the cytoplasmic domain. For example, Hirano et al showed that exchanging negatively charged amino acids for neutral ones made the KcsA channel insensitive to pH even though there were no amino-acid changes at the transmembrane region. [7] [8]

The KcsA channel is blocked by Cs+ ions and gating requires the presence of Mg2+ ions [9].


Structure

The structure of KcsA is that of a truncated cone, with a central pore running down the centre. The cone is made up of the M1 and M2 helices, which span the lipid bilayer. The wider end of the cone corresponds to the extracellular mouth of the channel. This envelops the pore (P) region, made up of the P-helices, plus a selectivity filter that is formed by a TVGYG sequence motif characteristic of potassium channels. Beneath the selectivity filter is a central water-filled cavity. Finally, the pore-lining M2 helices constrict the intracellular mouth to form a putative gate region.

The KcsA channel is considered a model channel because the KcsA structure provides a framework for the understanding of Potassium selectivity and permeation and because it appears that the structure of this pore domain is conserved between diverse Potassium channels from sequence comparisons.

The X-ray structure of KcsA reveals that there are two potassium ions within the selectivity filter (probably with a water molecule in between them), as well as a third Potassium ion in the central cavity. However, a crystal structure inevitably provides a static, spatially and temporally averaged image of a channel. To bridge the gap between molecular structure and physiological behavior an understanding of the atomic resolution dynamics of potassium channels is required. One way in which to approach this is via simulation studies. Simulations reveal that interactions of potassium ions and water with the KcsA channel at both the selectivity filter and at the intracellular gate are dynamic. [10]

An aspect of KcsA that has not been fully addressed by simulation studies is that the crystal structure appears to be that of the ‘closed' form of the channel. This is reasonable as the closed state of the channel is favored at neutral pH, at which the crystal structure was solved. Electronic paramagnetic resonance (EPR) spectroscopic studies of KcsA suggest that channel opening is associated with changes in packing of the transmembrane helices, so as to widen the pore at its intracellular mouth. [11]


The selectivity Filter

The X-ray structure of the KcsA Potassium channel revealed that selectivity filter is lined by backbone carbonyl groups from the residues of signature amino acid sequence TTVGYG, common to all known potassium channels [12]. A dehydrated potassium ion fits in the narrow selectivity filter precisely so that the energetic costs and gains are well balanced. The main chain carbonyl oxygen atoms that make up the selectivity filter are held at a precise position that allows them to substitute for water molecules in the hydrated shell of the 1.33 Ã… Potassium ion, but they are too far from the 0.95 Ã… Sodium ion, which thereby retains its hydration reaction shell and is blocked from traversing the pore. These observations led to a commonly accepted explanation of ion selectivity, which assumes that structural changes play the dominant role.[13] [14]

The selectivity filter of KcsA is formed by the backbone from four independent subunits usually labeled S1 to S4 starting at the extracellular side. The subunits are not bound directly to one another, and the result is a fairly flexible (liquid-like) pore structure.[15]


KcsA in Art

Roderick MacKinnon commissioned Birth of an Idea, a 5-foot (1.5 m) tall sculpture based on the KcsA potassium channel.[16] The artwork contains a wire object representing the channel's interior with a blown glass object representing the main cavity of the channel structure.



References

  1. ^ H.Schrempf1, O.Schmidt, R.Kummerlen, S.Hinnah2, D.Muller, M.Betzler, T.Steinkamp2 and R.Wagner A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans
  2. ^ B. Roux, Ion conduction and selectivity in K+ channels, Annu. Rev. Biophys. Biomol. Struct. 34 (2005) 153–171
  3. ^ Z. Lu, A.M. Klem, Y. Ramu, Ion conduction pore is conserved among potassium channels, Nature 413 (2001) 809–813.
  4. ^ S. Choe, Potassium channel structures, Nat.Rev.Neurosci. 3 (2002) 115–121
  5. ^ Cuello, L. G., J. G. Romero, ., E. Perozo. 1998. pH-dependent gating in the Streptomyces lividans K+ channel. Biochemistry. 37:3229–3236
  6. ^ Heginbotham, L., M. LeMasurier, ., C. Miller. 1999. Single streptomyces lividans K(+) channels: functional asymmetries and sidedness of proton activation. J. Gen. Physiol. 114:551–560
  7. ^ Minako Hirano, Yukiko Onishi, Toshio Yanagida, and Toru Ide. Role of the KcsA Channel Cytoplasmic Domain in pH-Dependent Gating. Biophysical Journal 101 (2011) 2157–2162
  8. ^ Yuchi, Z., V. P. Pau, and D. S. Yang. 2008. GCN4 enhances the stability of the pore domain of potassium channel KcsA. FEBS J. 275:6228– 6236
  9. ^ H.Schrempf1, O.Schmidt, R.Kummerlen, S.Hinnah2, D.Muller, M.Betzler, T.Steinkamp2 and R.Wagner A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans
  10. ^ M.S.P. Sansom, I.H. Shrivastava, K.M. Ranatunga and G. R. Smith. Simulations of ion channels- watching ions and water move. Trends Biochem Sci (2000) 25 368-374
  11. ^ D.A. Doyle, J. Morais Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Cahit, R. MacKinnon, The structure of the potassium channel: molecular basis of K+ conduction and selectivity, Science 280 (1998) 69–77
  12. ^ D.A. Doyle, J. Morais Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Cahit, R. MacKinnon, The structure of the potassium channel: molecular basis of K+ conduction and selectivity, Science 280 (1998) 69–77
  13. ^ D.A. Doyle, J. Morais Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Cahit, R. MacKinnon, The structure of the potassium channel: molecular basis of K+ conduction and selectivity, Science 280 (1998) 69–77
  14. ^ B. Hille, C.M. Armstrong, R. MacKinnon, Ion channels: from idea to reality, Nat. Med. 5 (1999) 1105–1109.
  15. ^ Sergei Yu. Noskov 1 , Benoît Roux. Ion selectivity in potassium channels. Biophysical Chemistry 124 (2006) 279 – 291
  16. ^ Ball, Philip (March 2008). "The crucible: Art inspired by science should be more than just a pretty picture". Chemistry World 5 (3): 42–43. http://www.rsc.org/chemistryworld/Issues/2008/March/ColumnThecrucible.asp. Retrieved 2009-01-12.

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This is the Wikipedia entry entitled "Voltage-gated potassium channel". More...

Voltage-gated potassium channel Edit Wikipedia article

The voltage-gated K+ channels that provide the outward currents of action potentials have similarities to bacterial K+ channels. These channels have been studied by X-ray diffraction, allowing determination of structural features at atomic resolution. The function of these channels is explored by electrophysiological studies. Genetic approaches include screening for behavioral changes in animals with mutations in K+ channel genes. Such genetic methods allowed the genetic identification of the "Shaker" K+ channel gene in Drosophila before ion channel gene sequences were well known. Study of the altered properties of voltage-gated K+ channel proteins produced by mutated genes has helped reveal the functional roles of K+ channel protein domains and even individual amino acids within their structures.

Voltage-gated K+ channels of vertebrates typically have four protein subunits arranged as a ring, each contributing to the wall of the trans-membrane K+ pore. There are six major α-helical sequences in each subunit. Some of these are hydrophobic transmembrane sequences.

Voltage-gated K+ channels are selective for K+ over other cations such as Na+. There is a selectivity filter at the narrowest part of the transmembrane pore. Channel mutation studies revealed the parts of the subunits that are essential for ion selectivity. They include the amino acid sequence (Thr-Val-Gly-Tyr-Gly) or (Thr-Val-Gly-Phe-Gly) typical to the selectivity filter of voltage-gated K+ channels. As K+ passes through the pore, interactions between potassium ions and water molecules are prevented and the K+ interacts with specific atomic components of the Thr-Val-Gly-X-Gly sequences from the four channel subunits[1].

Attempts continue to relate the structure of the mammalian voltage-gated K+ channel to its ability to respond to the voltage that exists across the membrane[2]. Specific domains of the channel subunits have been identified that are important for voltage-sensing and converting between the open conformation of the channel and closed conformations. There are at least two closed conformations; in one, the channel can open if the membrane potential becomes positive inside. Voltage-gated K+ channels inactivate after opening, entering a distinctive, second closed conformation. In the inactivated conformation, the channel cannot open, even if the transmembrane voltage is favorable. A domain at one end of the K+ channel protein mediates inactivation. This end of the protein can transiently plug the inner opening of the pore, preventing ion movement through the channel.

See also

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Ion channel Provide feedback

This family includes the two membrane helix type ion channels found in bacteria.

Literature references

  1. Choe S; , Nat Rev Neurosci 2002;3:115-121.: Potassium channel structures. PUBMED:11836519 EPMC:11836519


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR013099

This domain is found in a variety of potassium channel proteins, including the two membrane helix type ion channels found in bacteria [ PUBMED:11836519 ].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Ion_channel (CL0030), which has the following description:

This superfamily contains a diverse range of ion channels that share a pair of transmembrane helices in common. This clan is classified as the VIC (Voltage-gated Ion Channel) superfamily in TCDB.

The clan contains the following 8 members:

Ion_trans Ion_trans_2 IRK KdpA Lig_chan PKD_channel Polycystin_dom TrkH

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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  Seed
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Full
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(8643)
RP35
(18033)
RP55
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RP75
(47739)
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Full
(38525)
Representative proteomes UniProt
(92040)
RP15
(8643)
RP35
(18033)
RP55
(34023)
RP75
(47739)
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  Seed
(96)
Full
(38525)
Representative proteomes UniProt
(92040)
RP15
(8643)
RP35
(18033)
RP55
(34023)
RP75
(47739)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_55 (release 15.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 96
Number in full: 38525
Average length of the domain: 81.5 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 22.27 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.5 22.5
Trusted cut-off 22.5 22.5
Noise cut-off 22.4 22.4
Model length: 79
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Ion_trans_2 domain has been found. There are 694 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044R624 View 3D Structure Click here
A0A044R6Q6 View 3D Structure Click here
A0A044R891 View 3D Structure Click here
A0A044RBI9 View 3D Structure Click here
A0A044RD91 View 3D Structure Click here
A0A044RI64 View 3D Structure Click here
A0A044S914 View 3D Structure Click here
A0A044SHY6 View 3D Structure Click here
A0A044SJ06 View 3D Structure Click here
A0A044SWA6 View 3D Structure Click here
A0A044SWJ1 View 3D Structure Click here
A0A044T8I6 View 3D Structure Click here
A0A044T8Q4 View 3D Structure Click here
A0A044TIH4 View 3D Structure Click here
A0A044TPV7 View 3D Structure Click here
A0A044TZR8 View 3D Structure Click here
A0A044U972 View 3D Structure Click here
A0A044UE92 View 3D Structure Click here
A0A044UFN4 View 3D Structure Click here
A0A044UPN7 View 3D Structure Click here
A0A044URH8 View 3D Structure Click here
A0A044URI1 View 3D Structure Click here
A0A044UXN9 View 3D Structure Click here
A0A044V406 View 3D Structure Click here
A0A044V410 View 3D Structure Click here
A0A044V711 View 3D Structure Click here
A0A044V983 View 3D Structure Click here
A0A044VHP8 View 3D Structure Click here
A0A077YW62 View 3D Structure Click here
A0A077YWT5 View 3D Structure Click here
A0A077YWU4 View 3D Structure Click here
A0A077YWV2 View 3D Structure Click here
A0A077YYA2 View 3D Structure Click here
A0A077YYM6 View 3D Structure Click here
A0A077YZ43 View 3D Structure Click here
A0A077Z026 View 3D Structure Click here
A0A077Z0Y7 View 3D Structure Click here
A0A077Z2N8 View 3D Structure Click here
A0A077Z352 View 3D Structure Click here
A0A077Z3G7 View 3D Structure Click here