PDBsum entry 2bob

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protein ligands metals Protein-protein interface(s) links
Immune system/transport protein PDB id
Protein chains
219 a.a. *
212 a.a. *
103 a.a. *
Waters ×56
* Residue conservation analysis
PDB id:
Name: Immune system/transport protein
Title: Potassium channel kcsa-fab complex in thallium with tetrabutylammonium (tba)
Structure: Antibody fab fragment heavy chain. Chain: a. Antibody fab fragment light chain. Chain: b. Potassium channel kcsa. Chain: c. Fragment: residues 1-124. Engineered: yes. Mutation: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Streptomyces lividans. Organism_taxid: 1916. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.76Å     R-factor:   0.222     R-free:   0.251
Authors: M.J.Lenaeus,M.Vamvouka,P.J.Focia,A.Gross
Key ref:
M.J.Lenaeus et al. (2005). Structural basis of TEA blockade in a model potassium channel. Nat Struct Mol Biol, 12, 454-459. PubMed id: 15852022 DOI: 10.1038/nsmb929
09-Apr-05     Release date:   27-Apr-05    
Go to PROCHECK summary

Protein chain
No UniProt id for this chain
Struc: 219 a.a.
Protein chain
No UniProt id for this chain
Struc: 212 a.a.
Protein chain
Pfam   ArchSchema ?
P0A334  (KCSA_STRLI) -  pH-gated potassium channel KcsA
160 a.a.
103 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     voltage-gated potassium channel complex   1 term 
  Biological process     potassium ion transport   1 term 
  Biochemical function     voltage-gated potassium channel activity     1 term  


DOI no: 10.1038/nsmb929 Nat Struct Mol Biol 12:454-459 (2005)
PubMed id: 15852022  
Structural basis of TEA blockade in a model potassium channel.
M.J.Lenaeus, M.Vamvouka, P.J.Focia, A.Gross.
Potassium channels catalyze the selective transfer of potassium across the cell membrane and are essential for setting the resting potential in cells, controlling heart rate and modulating the firing pattern in neurons. Tetraethylammonium (TEA) blocks ion conduction through potassium channels in a voltage-dependent manner from both sides of the membrane. Here we show the structural basis of TEA blockade by cocrystallizing the prokaryotic potassium channel KcsA with two selective TEA analogs. TEA binding at both sites alters ion occupancy in the selectivity filter; these findings underlie the mutual destabilization and voltage-dependence of TEA blockade. We propose that TEA blocks potassium channels by acting as a potassium analog at the dehydration transition step during permeation.
  Selected figure(s)  
Figure 1.
Figure 1. Mechanism of permeation in potassium channels. (a) Two diagonal subunits of KcsA with the selectivity filter highlighted in black (residues 74 -80). Potassium ions are green spheres. (b) Model of permeation29. The selectivity filter is shown schematically with ions numbered 1 -4. Oxygen ligands are red crosses (water) or circles (carbonyl or hydroxyl). The two states of the selectivity filter (1/3 and 2/4) are occupied alternatively during permeation. A dehydration transition site for potassium is observed experimentally on the outside of the channel, but not on the inside (green arrow). (c) Structure of the selectivity filter in low permeant ion concentration. Left, low potassium (PDB entry 1K4D). Residues Thr74 -Asp80 are in stick representation. Oxygen, nitrogen and carbon are red, blue and gray, respectively. Middle, low thallium (PDB entry 1R3K). Thallium ions are purple spheres. Right, schematic representation of the structure observed at low permeant ion concentration with one ion alternating between sites 1 and 4. (d) Structure of the selectivity filter in high permeant ion concentrations. Left, high potassium (PDB entry 1K4C). The residues in the selectivity filter are labeled at the carbonyl level. Middle, high thallium (PDB entry 1R3J). Right, schematic representation with two ions alternating between the 1/3 and 2/4 states. All figures were generated with MolScript42 and Raster3D^43.
Figure 4.
Figure 4. Mechanism of TEA blockade. (a) The selectivity filter in high potassium (PDB entry 1K4C) is shown. In cesium (PDB entry 1R3L), an additional ion-binding site is observed in the cavity32 and a cesium ion is shown as a yellow sphere at this position. Two TEA molecules are shown in the TBA and TEAs positions, respectively. Arrows point to the external dehydration transition site observed in potassium and to the internal dehydration transition site observed in cesium. (b) Model of blockade. The selectivity filter is shown schematically with thallium ions drawn as filled circles and TEA as open circles. Binding of TEA stabilizes the close ion and destabilizes the remote ion. The observed states are highlighted. In the case of internal TEA binding, the external pore collapses to form the proposed inactivated state. (c) Stereo view down the four-fold axis onto the external TEA site. Four TEA molecules and their ligands were extracted from CPS (PDB entry 1A9X) and superimposed by least-squares fitting the TEA molecules. All possible orientations of the TEA-ligand cloud were generated and docked into the TEAs structure by a least-squares fit of the CPS TEA to TEAs. Oxygen ligands of TEA are red, nitrogen ligands are blue and chloride ions are green. KcsA residues of the external pore are shown. Arrows identify carbonyl oxygen atoms and the van der Waals contact between TEA and Tyr82. (d) View up the symmetry axis onto the internal TEA site. The same TEA-ligand structure as in c was docked into the TBA structure by a least-squares fit. Arrows identify carbonyl and hydroxyl oxygen atoms.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 454-459) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23262489 D.J.Posson, J.G.McCoy, and C.M.Nimigean (2013).
The voltage-dependent gate in MthK potassium channels is located at the selectivity filter.
  Nat Struct Mol Biol, 20, 159-166.
PDB codes: 4hyo 4hz3
21220117 C.Boiteux, and S.Bernèche (2011).
Absence of ion-binding affinity in the putatively inactivated low-[K+] structure of the KcsA potassium channel.
  Structure, 19, 70-79.  
21186363 S.Chakrapani, J.F.Cordero-Morales, V.Jogini, A.C.Pan, D.M.Cortes, B.Roux, and E.Perozo (2011).
On the structural basis of modal gating behavior in K(+) channels.
  Nat Struct Mol Biol, 18, 67-74.
PDB codes: 3or6 3or7
  20805574 A.Al-Sabi, O.Shamotienko, S.N.Dhochartaigh, N.Muniyappa, M.Le Berre, H.Shaban, J.Wang, J.T.Sack, and J.O.Dolly (2010).
Arrangement of Kv1 alpha subunits dictates sensitivity to tetraethylammonium.
  J Gen Physiol, 136, 273-282.  
19950367 E.J.Denning, and T.B.Woolf (2010).
Cooperative nature of gating transitions in K(+) channels as seen from dynamic importance sampling calculations.
  Proteins, 78, 1105-1119.  
20146057 E.Vales, and M.Raja (2010).
The "flipped" state in E71A-K+-channel KcsA exclusively alters the channel gating properties by tetraethylammonium and phosphatidylglycerol.
  J Membr Biol, 234, 1.  
20339151 F.ten Hoopen, T.A.Cuin, P.Pedas, J.N.Hegelund, S.Shabala, J.K.Schjoerring, and T.P.Jahn (2010).
Competition between uptake of ammonium and potassium in barley and Arabidopsis roots: molecular mechanisms and physiological consequences.
  J Exp Bot, 61, 2303-2315.  
21037567 R.J.Hilf, C.Bertozzi, I.Zimmermann, A.Reiter, D.Trauner, and R.Dutzler (2010).
Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel.
  Nat Struct Mol Biol, 17, 1330-1336.
PDB codes: 2xq3 2xq4 2xq5 2xq6 2xq7 2xq8 2xq9 2xqa
  19917730 C.A.Ahern, A.L.Eastwood, D.A.Dougherty, and R.Horn (2009).
An electrostatic interaction between TEA and an introduced pore aromatic drives spring-in-the-door inactivation in Shaker potassium channels.
  J Gen Physiol, 134, 461-469.  
19661921 C.Ader, R.Schneider, S.Hornig, P.Velisetty, V.Vardanyan, K.Giller, I.Ohmert, S.Becker, O.Pongs, and M.Baldus (2009).
Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity.
  EMBO J, 28, 2825-2834.  
19834614 F.C.Chatelain, S.Gazzarrini, Y.Fujiwara, C.Arrigoni, C.Domigan, G.Ferrara, C.Pantoja, G.Thiel, A.Moroni, and D.L.Minor (2009).
Selection of inhibitor-resistant viral potassium channels identifies a selectivity filter site that affects barium and amantadine block.
  PLoS One, 4, e7496.  
19482941 I.Kopljar, A.J.Labro, E.Cuypers, H.W.Johnson, J.D.Rainier, J.Tytgat, and D.J.Snyders (2009).
A polyether biotoxin binding site on the lipid-exposed face of the pore domain of Kv channels revealed by the marine toxin gambierol.
  Proc Natl Acad Sci U S A, 106, 9896-9901.  
  19917731 R.Olcese (2009).
It's spring-time for slow inactivation.
  J Gen Physiol, 134, 457-459.  
19915587 Y.Xu, H.G.Shin, S.Szép, and Z.Lu (2009).
Physical determinants of strong voltage sensitivity of K(+) channel block.
  Nat Struct Mol Biol, 16, 1252-1258.
PDB code: 3k6n
  19332619 Z.Wang, N.C.Wong, Y.Cheng, S.J.Kehl, and D.Fedida (2009).
Control of voltage-gated K+ channel permeability to NMDG+ by a residue at the outer pore.
  J Gen Physiol, 133, 361-374.  
18488040 C.Ader, R.Schneider, S.Hornig, P.Velisetty, E.M.Wilson, A.Lange, K.Giller, I.Ohmert, M.F.Martin-Eauclaire, D.Trauner, S.Becker, O.Pongs, and M.Baldus (2008).
A structural link between inactivation and block of a K+ channel.
  Nat Struct Mol Biol, 15, 605-612.  
18636331 D.B.Tikhonov (2008).
Mechanisms of action of ligands of potential-dependent sodium channels.
  Neurosci Behav Physiol, 38, 461-469.  
18476673 H.Wulff, and B.S.Zhorov (2008).
K+ channel modulators for the treatment of neurological disorders and autoimmune diseases.
  Chem Rev, 108, 1744-1773.  
17369424 A.J.Oseguera, L.D.Islas, R.García-Villegas, and T.Rosenbaum (2007).
On the mechanism of TBA block of the TRPV1 channel.
  Biophys J, 92, 3901-3914.  
17496040 D.B.Tikhonov, and B.S.Zhorov (2007).
Sodium channels: ionic model of slow inactivation and state-dependent drug binding.
  Biophys J, 93, 1557-1570.  
17704175 G.Gibor, D.Yakubovich, A.Rosenhouse-Dantsker, A.Peretz, H.Schottelndreier, G.Seebohm, N.Dascal, D.E.Logothetis, Y.Paas, and B.Attali (2007).
An inactivation gate in the selectivity filter of KCNQ1 potassium channels.
  Biophys J, 93, 4159-4172.  
  17438120 G.Panyi, and C.Deutsch (2007).
Probing the cavity of the slow inactivated conformation of shaker potassium channels.
  J Gen Physiol, 129, 403-418.  
17261195 I.Bruhova, and B.S.Zhorov (2007).
Monte Carlo-energy minimization of correolide in the Kv1.3 channel: possible role of potassium ion in ligand-receptor interactions.
  BMC Struct Biol, 7, 5.  
17342721 J.D.Faraldo-Gómez, and B.Roux (2007).
Characterization of conformational equilibria through Hamiltonian and temperature replica-exchange simulations: assessing entropic and environmental effects.
  J Comput Chem, 28, 1634-1647.  
17922012 J.F.Cordero-Morales, V.Jogini, A.Lewis, V.Vásquez, D.M.Cortes, B.Roux, and E.Perozo (2007).
Molecular driving forces determining potassium channel slow inactivation.
  Nat Struct Mol Biol, 14, 1062-1069.  
17541576 M.Baldus (2007).
Magnetic resonance in the solid state: applications to protein folding, amyloid fibrils and membrane proteins.
  Eur Biophys J, 36, 37-48.  
17657566 M.Baldus (2007).
ICMRBS founder's medal 2006: biological solid-state NMR, methods and applications.
  J Biomol NMR, 39, 73-86.  
16612389 A.Lange, K.Giller, S.Hornig, M.F.Martin-Eauclaire, O.Pongs, S.Becker, and M.Baldus (2006).
Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR.
  Nature, 440, 959-962.  
  17130517 B.Roux (2006).
Extracellular blockade of potassium channels by TEA+: the tip of the iceberg?
  J Gen Physiol, 128, 635-636.  
  17130518 C.A.Ahern, A.L.Eastwood, H.A.Lester, D.A.Dougherty, and R.Horn (2006).
A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels.
  J Gen Physiol, 128, 649-657.  
  16885519 C.C.Canavier, and R.S.Landry (2006).
An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo.
  J Neurophysiol, 96, 2549-2563.  
  16940557 C.M.Wilkens, and R.W.Aldrich (2006).
State-independent block of BK channels by an intracellular quaternary ammonium.
  J Gen Physiol, 128, 347-364.  
  16847099 E.C.Ray, and C.Deutsch (2006).
A trapped intracellular cation modulates K+ channel recovery from slow inactivation.
  J Gen Physiol, 128, 203-217.  
  17043151 G.Panyi, and C.Deutsch (2006).
Cross talk between activation and slow inactivation gates of Shaker potassium channels.
  J Gen Physiol, 128, 547-559.  
  16606689 H.T.Kurata, L.J.Marton, and C.G.Nichols (2006).
The polyamine binding site in inward rectifier K+ channels.
  J Gen Physiol, 127, 467-480.  
16532009 J.F.Cordero-Morales, L.G.Cuello, Y.Zhao, V.Jogini, D.M.Cortes, B.Roux, and E.Perozo (2006).
Molecular determinants of gating at the potassium-channel selectivity filter.
  Nat Struct Mol Biol, 13, 311-318.
PDB codes: 1zwi 2atk
  16801385 J.T.Sack, and R.W.Aldrich (2006).
Binding of a gating modifier toxin induces intersubunit cooperativity early in the Shaker K channel's activation pathway.
  J Gen Physiol, 128, 119-132.  
16835240 M.Iwamoto, H.Shimizu, F.Inoue, T.Konno, Y.C.Sasaki, and S.Oiki (2006).
Surface structure and its dynamic rearrangements of the KcsA potassium channel upon gating and tetrabutylammonium blocking.
  J Biol Chem, 281, 28379-28386.  
  16636204 R.A.Piskorowski, and R.W.Aldrich (2006).
Relationship between pore occupancy and gating in BK potassium channels.
  J Gen Physiol, 127, 557-576.  
16272446 S.S.Deol, C.Domene, P.J.Bond, and M.S.Sansom (2006).
Anionic phospholipid interactions with the potassium channel KcsA: simulation studies.
  Biophys J, 90, 822-830.  
  16043774 H.G.Shin, Y.Xu, and Z.Lu (2005).
Evidence for sequential ion-binding loci along the inner pore of the IRK1 inward-rectifier K+ channel.
  J Gen Physiol, 126, 123-135.  
16301524 L.Gao, X.Mi, V.Paajanen, K.Wang, and Z.Fan (2005).
Activation-coupled inactivation in the bacterial potassium channel KcsA.
  Proc Natl Acad Sci U S A, 102, 17630-17635.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.