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1.A.1.9.3
Neuronal 2-P (4 TMS) domain K+ membrane tension-gated channel, TRAAK (stimulated by arachidonic acid and polyunsaturated fatty acids (Fink et al., 1998). The crystal structures of conductive and nonconductive human K2P TRAAK K+ channel has been solved (Brohawn et al., 2012; Brohawn et al. 2014). Regulated by mechanical deformation of the membrane and temperature as well as polyunsaturated fatty acids (Brohawn et al., 2012). Multiple modalities converge on a common gate to control K2P channel function (Bagriantsev et al., 2011).  In the non-conductive state, a lipid acyl chain accesses the channel cavity through a 5 Å-wide lateral opening in the membrane inner leaflet and physically blocks ion passage. In the conductive state, rotation of transmembrane helix 4 about a central hinge seals the intramembrane opening, preventing lipid block of the cavity and permitting ion entry. Additional rotation of a membrane interacting TM2-TM3 segment, unique to mechanosensitive K2Ps, against TM4 may further stabilize the conductive conformation. Comparison of the structures provodes a biophysical explanation for TRAAK mechanosensitivity--an expansion in cross-sectional area up to 2.7 nm2 in the conductive state is expected to create a membrane-tension-dependent energy difference between conformations that promotes force activation (Brohawn et al. 2014).  TM helix straightening and buckling may underlie channel activation (Lolicato et al. 2014). A lipid chain blocks the conducting path in the clBrohawn et al. 2014). Regulated by mechanical deformation of the membrane and temperature as well as polyunsaturated fatty acids (Brohawn et al., 2012). Multiple modalities converge on a common gate to control K2P channel function (Bagriantsev et al., 2011).  In the non-conductive state, a lipid acyl chain accesses the channel cavity through a 5 Å-wide lateral opening in the membrane inner leaflet and physically blocks ion passage. In the conductive state, rotation of transmembrane helix 4 about a central hinge seals the intramembrane opening, preventing lipid block of the cavity and permitting ion entry. Additional rotation of a membrane interacting TM2-TM3 segment, unique to mechanosensitive K2Ps, against TM4 may further stabilize the conductive conformation. Comparison of the structures provodes a biophysical explanation for TRAAK mechanosensitivity--an expansion in cross-sectional area up to 2.7 nm2 in the conductive state is expected to create a membrane-tension-dependent energy difference between conformations that promotes force activation (Brohawn et al. 2014).  TM helix straightening and buckling may underlie channel activation (Lolicato et al. 2014). A lipid chain blocks the conducting path in the clBrohawn et al. 2014).  TM helix straightening and buckling may underlie channel activation (Lolicato et al. 2014). A lipid chain blocks the conducting path in the closed state (Rasmussen 2016).

Accession Number:O88454
Protein Name:Potassium channel subfamily K member 4 aka Kcnk4 aka Traak
Length:398
Molecular Weight:43052.00
Species:Mus musculus (Mouse) [10090]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

Genevestigator: O88454
eggNOG: roNOG08342
HEGENOM: HBG717586
RefSeq: NP_032457.1   
Entrez Gene ID: 16528   
Pfam: PF07885   
KEGG: mmu:16528   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005267 F:potassium channel activity
GO:0005244 F:voltage-gated ion channel activity
GO:0006813 P:potassium ion transport

References (2)

[1] “A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids.”  Fink M.et.al.   9628867
[2] “Inhalational anesthetics activate two-pore-domain background K+ channels.”  Patel A.J.et.al.   10321245

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MRSTTLLALL ALVLLYLVSG ALVFQALEQP HEQQAQKKMD HGRDQFLRDH PCVSQKSLED 
61:	FIKLLVEALG GGANPETSWT NSSNHSSAWN LGSAFFFSGT IITTIGYGNI VLHTDAGRLF 
121:	CIFYALVGIP LFGMLLAGVG DRLGSSLRRG IGHIEAIFLK WHVPPGLVRS LSAVLFLLIG 
181:	CLLFVLTPTF VFSYMESWSK LEAIYFVIVT LTTVGFGDYV PGDGTGQNSP AYQPLVWFWI 
241:	LFGLAYFASV LTTIGNWLRA VSRRTRAEMG GLTAQAASWT GTVTARVTQR TGPSAPPPEK 
301:	EQPLLPSSLP APPAVVEPAG RPGSPAPAEK VETPSPPTAS ALDYPSENLA FIDESSDTQS 
361:	ERGCALPRAP RGRRRPNPSK KPSRPRGPGR LRDKAVPV