1.A.1.1.1 Two TMS K+ and water channel (conducts K+ (KD = 8 mM); blocked by Na+ (190 mM) (Renart et al., 2006) and tetrabutylammonium (Iwamoto et al., 2006)). Ion permeation occurs by ion-ion contacts in single file fashion through the selectivity filter (Köpfer et al. 2014). A narrow pore lined with four arrays of carbonyl groups is responsible for
ion selectivity, whereas a conformational change of the four inner transmembrane helices (TMS2) is
involved in gating (Baker et al. 2007). Two gates have been identified; one is located at the inner bundle crossing and is activated by H+ while the second gate is in the selectivity filter (Rauh et al. 2017). The C-terminal domain mediates pH modulation (Hirano et al., 2011; Pau et al., 2007). KcsA exhibits a global twisting motion upon gating (Shimizu et al., 2008). Activity is influenced by the phase of the lipid bilayer (Seeger et al. 2010), and occupancy of nonannular lipid binding sites increases the stability of the tetrameric complex (Triano et al. 2010). The open conformation of KcsA can disturb the bilayer integrity and catalyze the flipping of
phospholipids (Nakao et al. 2014). This protein is identical to the KcsA orthologue (P0A333) in Streptomyces coelicolor. The stability of the pre domain in KcsA is stabilized by GCN4 (Yuchi et al. 2008). The
potential role of pore hydration in channel gating has been evaluated (Blasic et al. 2015). Having multiple K+ ions bound simultaneously
is required for selective K+ conduction, and a reduction in the number of bound K+ ions
destroys the multi-ion selectivity mechanism utilized by K+ channels (Medovoy et al. 2016). The channel accomodates K+ and H2O molecules alternately in a K+-H2O-K+-H2O series through the channel (Kratochvil et al. 2016). Insertion of KcsA is spontaneous and directional as the
cytosolic part of the protein does not translocate across the membrane barrier. Charged residues, not hydrophobic residues, are crucial for insertion of the unfolded protein
into the membrane via electrostatic interactions between
membrane and protein. A two-step
mechanism was proposed. An initial electrostatic attraction between membrane and protein
represents the first step prior to insertion of hydrophobic residues into the hydrocarbon core of
the membrane (Altrichter et al. 2016). Bend, splay, and twist distinguish KcsA gate opening, filter opening, and filter-gate coupling, respectively (Mitchell and Leibler 2017). Details of the water permeability have been presented. Water flow through KcsA is halved by 200 mM K+ in the aqueous
solution, which indicates an effective K+ dissociation constant in
that range for a singly occupied channel. (Hoomann et al. 2013). A parameterized MARTINI program can be used to predict the hinging motions of the protein (Li et al. 2019). Activation of KcsA is initiated by proton binding to the pH gate upon an intracellular drop in pH which prompts a conformational switch, leading to a loss of affinity for potassium ions at the selectivity filter and therefore to channel inactivation (Rivera-Torres et al. 2016). An alteration in the conformational equilibrium of the intracellular K+-gate is one of the fundamental mechanisms underlying the dysfunctions of K+ channels caused by disease-related mutations (Iwahashi et al. 2020). Folding and misfolding of KcsA monomers during assembly and tetramerization has been examined (Song et al. 2021). The flexible C-terminus stabilizes KcsA tetramers at a neutral pH with decreased stabilization at acidic pH (Howarth and McDermott 2022).
|
Accession Number: | P0A334 |
Protein Name: | Voltage-gated potassium channel |
Length: | 160 |
Molecular Weight: | 17694.00 |
Species: | streptomyces lividans [1916] |
Number of TMSs: | 2 |
Location1 / Topology2 / Orientation3: |
Cell membrane1 / Multi-pass membrane protein2 |
Substrate |
potassium(1+), water |
---|
DIP: |
DIP-29626N
|
Pfam: |
PF07885
|
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[1] “A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans.” Schrempf H. et.al. 7489706
[2] “Proteomics on full-length membrane proteins using mass spectrometry.” le Coutre J. et.al. 10757971
[3] “Single potassium ion seeks open channel for transmembrane travels: tales from the KcsA structure.” Gouaux E. et.al. 9782060
[4] “The structure of the potassium channel: molecular basis of K+ conduction and selectivity.” Doyle D.A. et.al. 9525859
[5] “Molecular architecture of full-length KcsA: role of cytoplasmic domains in ion permeation and activation gating.” Cortes D.M. et.al. 11158168
[6] “Structure of the KcsA channel intracellular gate in the open state.” Liu Y.-S. et.al. 11573095
[7] “Energetic optimization of ion conduction rate by the K+ selectivity filter.” Morais-Cabral J.H. et.al. 11689935
[8] “Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.” Zhou Y. et.al. 11689936
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1: MPPMLSGLLA RLVKLLLGRH GSALHWRAAG AATVLLVIVL LAGSYLAVLA ERGAPGAQLI
61: TYPRALWWSV ETATTVGYGD LYPVTLWGRL VAVVVMVAGI TSFGLVTAAL ATWFVGREQE
121: RRGHFVRHSE KAAEEAYTRT TRALHERFDR LERMLDDNRR