User:Lori Wetmore/Sandbox 2
From Proteopedia
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==Selecvitity Filter/s== | ==Selecvitity Filter/s== | ||
| + | Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by five residues (TVGYG-in prokaryotic species) in the P loop from each subunit which have their electro-negative carbonyl oxygen atoms aligned towards the centre of the filter pore and form an anti-prism similar to a water solvating shell around each potassium binding site. The distance between the carbonyl oxygens and potassium ions in the binding sites of the selectivity filter is the same as between water oxygens in the first hydration shell and a potassium ion in water solution. Passage of sodium ions would be energetically unfavorable since the strong interactions between the filter and pore helix would prevent the channel from collapsing to the smaller sodium ion size. The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in KcsA). The next residue towards the extracellular side of the protein is the negatively charged Asp80 (KcsA). This residue together with the five filter residues form the pore that connects the water filled cavity in the centre of the protein with the extracellular solution.[12] | ||
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| + | The carbonyl oxygens are strongly electro-negative and cation attractive. The filter can accommodate potassium ions at 4 sites usually labelled S1 to S4 starting at the extracellular side. In addition one ion can bind in the cavity at a site called SC or one or more ions at the extracellular side at more or less well defined sites called S0 or Sext. Several different occupancies of these sites are possible. Since the X-ray structures are averages over many molecules, it is, however, not possible to deduce the actual occupancies directly from such a structure. In general, there is some disadvantage due to electrostatic repulsion to have two neighbouring sites occupied by ions. The mechanism for ion translocation in KcsA has been studied extensively by simulation techniques. A complete map of the free energies of the 24=16 states (characterised by the occupancy of the S1, S2, S3 and S4 sites) has been calculated with molecular dynamics simulations resulting in the prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role. The two extracellular states, Sext and S0, were found in a better resolved structure of KcsA at high potassium concentration. In free energy calculations the entire ionic pathway from the cavity, through the four filter sites out to S0 and Sext was covered in MD simulations. The amino acids sequence of the selectivity filter of potassium ion channels is conserved with the exception that an isoleucine residue in eukaryotic potassium ion channels often is substituted with a valine residue in prokaryotic channels.[12] | ||
==Channel Function== | ==Channel Function== | ||
Revision as of 20:59, 3 October 2010
Look for a family of channels (ion or otherwise) or transporters.
I'm going to discuss the family of potassium ion channels, and the specific channel I'll be using to illustrate will be the KcsA potassium ion channel. (http://www.rcsb.org/pdb/explore/explore.do?structureId=1k4c) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2383984/ http://www.ks.uiuc.edu/Research/smd_imd/kcsa/ http://jgp.rupress.org/content/128/5/569.long http://www.ncbi.nlm.nih.gov/pubmed/18621821 http://ion.ucdavis.edu/pdfs/bj02-KcsA.pdf http://ion.ucdavis.edu/pdfs/kchan1.pdf http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=12521
Here are just a few of the things that I'll want to incorporate into my page at some point:
When viewed in (where the N-terminus is gradually shaded into the C-terminus according to the scale below)
| N | C |
|
Contents |
KcsA: A K+ channel
Potassium, a major cation in most cells, is responsible (in addition to other cations such as sodium) for the creation of the cell membrane potential, which is responsible for the generation of an action potential, which is necessary for a number of cellular functions such as neurotransmission, muscle contraction, and heart function. The proper balance of potassium in the cell is maintained by potassium ion pumps in the cellular membrane. To date, there are five potassium ion channels with a resolved structure (KcsA, KirBac1.1, KirBac3.1, KvAP, MthK), with KirBac3.1 being the most recently resolved, and they are all tetramers with several conserved secondary structural elements. [1]
Channel Structure
As previously mentioned, potassium channels have a tetrameric structure in which four identical protein subunits associate to form a homotetramer, or a fourfold symmetric complex arranged around a central ion conducting pore. Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C4 symmetry. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selective permeability. There are over 80 mammalian genes that encode potassium channel subunits. However potassium channels found in bacteria are amongst the most studied of ion channels, in terms of their molecular structure. Using X-ray crystallography, [2] [3] profound insights have been gained into how potassium ions pass through these channels and why sodium ions, which are much smaller than potassium ions, do not. [4]
Selecvitity Filter/s
Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by five residues (TVGYG-in prokaryotic species) in the P loop from each subunit which have their electro-negative carbonyl oxygen atoms aligned towards the centre of the filter pore and form an anti-prism similar to a water solvating shell around each potassium binding site. The distance between the carbonyl oxygens and potassium ions in the binding sites of the selectivity filter is the same as between water oxygens in the first hydration shell and a potassium ion in water solution. Passage of sodium ions would be energetically unfavorable since the strong interactions between the filter and pore helix would prevent the channel from collapsing to the smaller sodium ion size. The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in KcsA). The next residue towards the extracellular side of the protein is the negatively charged Asp80 (KcsA). This residue together with the five filter residues form the pore that connects the water filled cavity in the centre of the protein with the extracellular solution.[12]
The carbonyl oxygens are strongly electro-negative and cation attractive. The filter can accommodate potassium ions at 4 sites usually labelled S1 to S4 starting at the extracellular side. In addition one ion can bind in the cavity at a site called SC or one or more ions at the extracellular side at more or less well defined sites called S0 or Sext. Several different occupancies of these sites are possible. Since the X-ray structures are averages over many molecules, it is, however, not possible to deduce the actual occupancies directly from such a structure. In general, there is some disadvantage due to electrostatic repulsion to have two neighbouring sites occupied by ions. The mechanism for ion translocation in KcsA has been studied extensively by simulation techniques. A complete map of the free energies of the 24=16 states (characterised by the occupancy of the S1, S2, S3 and S4 sites) has been calculated with molecular dynamics simulations resulting in the prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role. The two extracellular states, Sext and S0, were found in a better resolved structure of KcsA at high potassium concentration. In free energy calculations the entire ionic pathway from the cavity, through the four filter sites out to S0 and Sext was covered in MD simulations. The amino acids sequence of the selectivity filter of potassium ion channels is conserved with the exception that an isoleucine residue in eukaryotic potassium ion channels often is substituted with a valine residue in prokaryotic channels.[12]
Channel Function
Gating Mechanism
Ongoing Research
References
- ↑ Hellgren M, Sandberg L, Edholm O. A comparison between two prokaryotic potassium channels (KirBac1.1 and KcsA) in a molecular dynamics (MD) simulation study. Biophys Chem. 2006 Mar 1;120(1):1-9. Epub 2005 Oct 25. PMID:16253415 doi:10.1016/j.bpc.2005.10.002
- ↑ Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998 Apr 3;280(5360):69-77. PMID:9525859
- ↑ MacKinnon R, Cohen SL, Kuo A, Lee A, Chait BT. Structural conservation in prokaryotic and eukaryotic potassium channels. Science. 1998 Apr 3;280(5360):106-9. PMID:9525854
- ↑ Armstrong C. The vision of the pore. Science. 1998 Apr 3;280(5360):56-7. PMID:9556453
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.Zhou, Y., Morais-Cabral, J.H., Kaufman, A., MacKinnon, R. Journal: (2001) Nature 414: 43-48 PubMed: 11689936 View PubMed Abstract at NCBI DOI: 10.1038/35102009
