6W8C

K2P2.1 (TREK-1):ML335 complex, 1 mM K+


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted IEPClick on this verticalbar to view detailsBest fitted Q6FClick on this verticalbar to view detailsBest fitted B7GClick on this verticalbar to view detailsBest fitted R16Click on this verticalbar to view detailsBest fitted 11AClick on this verticalbar to view detailsBest fitted D12Click on this verticalbar to view detailsBest fitted UNDClick on this verticalbar to view details

This is version 1.2 of the entry. See complete history


Literature

K 2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.

Lolicato, M.Natale, A.M.Abderemane-Ali, F.Crottes, D.Capponi, S.Duman, R.Wagner, A.Rosenberg, J.M.Grabe, M.Minor Jr., D.L.

(2020) Sci Adv 6

  • DOI: https://doi.org/10.1126/sciadv.abc9174
  • Primary Citation of Related Structures:  
    6W7B, 6W7C, 6W7D, 6W7E, 6W82, 6W83, 6W84, 6W85, 6W86, 6W87, 6W88, 6W8A, 6W8C, 6W8F

  • PubMed Abstract: 

    K 2P potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric K 2P s is unknown. Here, combining K 2P 2.1 (TREK-1) x-ray crystallography in different potassium concentrations, potassium anomalous scattering, molecular dynamics, and electrophysiology, we uncover unprecedented, asymmetric, potassium-dependent conformational changes that underlie K 2P C-type gating. These asymmetric order-disorder transitions, enabled by the K 2P heterodimeric architecture, encompass pinching and dilation, disrupt the S1 and S2 ion binding sites, require the uniquely long K 2P SF2-M4 loop and conserved "M3 glutamate network," and are suppressed by the K 2P C-type gate activator ML335. These findings demonstrate that two distinct C-type gating mechanisms can operate in one channel and underscore the SF2-M4 loop as a target for K 2P channel modulator development.


  • Organizational Affiliation

    Cardiovascular Research Institute, University of California, San Francisco, CA 93858-2330, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Potassium channel subfamily K member 2
A, B
312Mus musculusMutation(s): 13 
Gene Names: Kcnk2
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P97438 (Mus musculus)
Explore P97438 
Go to UniProtKB:  P97438
IMPC:  MGI:109366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP97438
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 11 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IEP
Query on IEP

Download Ideal Coordinates CCD File 
AA [auth B],
L [auth A]
[(2~{S})-1-octadecanoyloxy-3-[oxidanyl-[(1~{R},2~{R},3~{S},4~{S},5~{S},6~{S})-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl] icosa-5,8,11,14-tetraenoate
C47 H85 O19 P3
CNWINRVXAYPOMW-UWUKCHIJSA-N
Q6F
Query on Q6F

Download Ideal Coordinates CCD File 
CA [auth B],
J [auth A]
N-[(2,4-dichlorophenyl)methyl]-4-[(methylsulfonyl)amino]benzamide
C15 H14 Cl2 N2 O3 S
RDFIQTZRJRVFHK-UHFFFAOYSA-N
B7G
Query on B7G

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K [auth A],
W [auth B],
X [auth B],
Y [auth B]
heptyl beta-D-glucopyranoside
C13 H26 O6
NIDYWHLDTIVRJT-UJPOAAIJSA-N
R16
Query on R16

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G [auth A],
H [auth A],
I [auth A]
HEXADECANE
C16 H34
DCAYPVUWAIABOU-UHFFFAOYSA-N
11A
Query on 11A

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BA [auth B],
M [auth A]
UNDECANOIC ACID
C11 H22 O2
ZDPHROOEEOARMN-UHFFFAOYSA-N
D12
Query on D12

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U [auth B],
V [auth B]
DODECANE
C12 H26
SNRUBQQJIBEYMU-UHFFFAOYSA-N
UND
Query on UND

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Z [auth B]UNDECANE
C11 H24
RSJKGSCJYJTIGS-UHFFFAOYSA-N
OCT
Query on OCT

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S [auth B],
T [auth B]
N-OCTANE
C8 H18
TVMXDCGIABBOFY-UHFFFAOYSA-N
CD
Query on CD

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P [auth B],
Q [auth B],
R [auth B]
CADMIUM ION
Cd
WLZRMCYVCSSEQC-UHFFFAOYSA-N
LNK
Query on LNK

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DA [auth B]PENTANE
C5 H12
OFBQJSOFQDEBGM-UHFFFAOYSA-N
K
Query on K

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C [auth A]
D [auth A]
E [auth A]
F [auth A]
N [auth A]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.129α = 90
b = 119.783β = 90
c = 128.872γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
GDAdata collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted IEPClick on this verticalbar to view detailsBest fitted Q6FClick on this verticalbar to view detailsBest fitted B7GClick on this verticalbar to view detailsBest fitted R16Click on this verticalbar to view detailsBest fitted 11AClick on this verticalbar to view detailsBest fitted D12Click on this verticalbar to view detailsBest fitted UNDClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)United StatesNIH-R01-MH093603

Revision History  (Full details and data files)

  • Version 1.0: 2021-01-27
    Type: Initial release
  • Version 1.1: 2023-10-18
    Changes: Data collection, Database references, Refinement description
  • Version 1.2: 2024-10-23
    Changes: Structure summary