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1.A.1.17.1
The archaeal voltage-regulated K channel, KvAP (Ruta et al., 2003). X-ray and solution structures are available. The latter shows phospholipid interactions with the isolated voltage sensor domain (Butterwick and MacKinnon 2010; Li et al. 2014). The gating-charge arginine in TMS4 of the voltage sensor forms part of the helical hairpin "paddle", and it moves 15-20 Å through the membrane to open the pore (Ruta et al., 2005). The orientation and depth of insertion of the voltage-sensing S4 helix has been determined (Doherty et al., 2010). A synthetic S6 segment derived from the KvAP channel self-assembles, permeabilizes lipid vesicles, and exhibits ion channel activity in bilayer lipid membrane (Verma et al., 2011).  Thus the gating mechanism combines structural rearrangements and electric-field remodeling ( Li et al. 2014).  KvAP has been reconstituted in Giant Unilamellar Vesicles (GUVs) (Garten et al. 2015).  TMS4 (S4) which senses voltage also promotes membrane insertion of the voltage-sensor domain (Mishima et al. 2016). KvAP has a configuration consistent with a water channel, possibly underlying the conductance of protons, and other cations, through voltage-sensor domains (Freites et al. 2006). The structural dynamics of the paddle motif loop in the activated conformation of the KvAP voltage sensor have been studied from biophysical standpoints (Das et al. 2019). The S4 alpha-helix, which is straight in the experimental crystal structure solved under depolarized conditions (Vm approximately 0), breaks into two segments when the cell membrane is hyperpolarized (Vm << 0) and reversibly forms a single straight helix following depolarization (Vm = 0) ((Bignucolo and Bernèche 2020). The outermost segment of S4 translates along the normal to the membrane, bringing new perspective to previously paradoxical accessibility experiments that were initially thought to imply the displacement of the whole VSD across the membrane. The breakage of S4 under (hyper)polarization could be a general feature of Kv channels with a non-swapped topology. The surface charge of the membrane does not significantly affect the topology and structural dynamics of the sensor loop in membranes (Das and Raghuraman 2021). The dynamic variability of the sensor loop is preserved in both zwitterionic (POPC) and anionic (POPC/POPG) lipid membranes. The lifetime distribution analysis for the NBD-labelled residues by the maximum entropy method (MEM) demonstrates that, in contrast to micelles, the membrane environment not only reduces the relative discrete population of sensor loop conformations, but also broadens the lifetime distribution peaks.

Accession Number:Q9YDF8
Protein Name:KvAP
Length:295
Molecular Weight:32535.00
Species:Aeropyrum pernix [56636]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

DIP: DIP-29648N
RefSeq: NP_147625.1   
Entrez Gene ID: 1445031   
Pfam: PF07885   
BioCyc: APER272557:APE0955-MONOMER   
KEGG: ape:APE_0955   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005886 C:plasma membrane
GO:0005267 F:potassium channel activity
GO:0005244 F:voltage-gated ion channel activity
GO:0006813 P:potassium ion transport

References (3)

[1] “Complete genome sequence of an aerobic hyper-thermophilic crenarchaeon, Aeropyrum pernix K1.”  Kawarabayasi Y.et.al.   10382966
[2] “Functional analysis of an archaebacterial voltage-dependent K+ channel.”  Ruta V.et.al.   12629550
[3] “X-ray structure of a voltage-dependent K(+) channel.”  Jiang Y.et.al.   12721618
Structure:
1ORQ   1ORS   2A0L   2KYH   6UWM     

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSVERWVFPG CSVMARFRRG LSDLGGRVRN IGDVMEHPLV ELGVSYAALL SVIVVVVEYT 
61:	MQLSGEYLVR LYLVDLILVI ILWADYAYRA YKSGDPAGYV KKTLYEIPAL VPAGLLALIE 
121:	GHLAGLGLFR LVRLLRFLRI LLIISRGSKF LSAIADAADK IRFYHLFGAV MLTVLYGAFA 
181:	IYIVEYPDPN SSIKSVFDAL WWAVVTATTV GYGDVVPATP IGKVIGIAVM LTGISALTLL 
241:	IGTVSNMFQK ILVGEPEPSC SPAKLAEMVS SMSEEEFEEF VRTLKNLRRL ENSMK