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- PDB-9u7f: structure of human KCNQ1-KCNE1-CaM complex -

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Basic information

Entry
Database: PDB / ID: 9u7f
Titlestructure of human KCNQ1-KCNE1-CaM complex
Components
  • (Potassium voltage-gated channel subfamily ...) x 2
  • Calmodulin-1
KeywordsMEMBRANE PROTEIN / Ion channels
Function / homology
Function and homology information


vestibular nucleus development / negative regulation of protein targeting to membrane / secretory granule organization / gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / lumenal side of membrane / negative regulation of voltage-gated potassium channel activity / rhythmic behavior ...vestibular nucleus development / negative regulation of protein targeting to membrane / secretory granule organization / gastrin-induced gastric acid secretion / corticosterone secretion / voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization / basolateral part of cell / lumenal side of membrane / negative regulation of voltage-gated potassium channel activity / rhythmic behavior / stomach development / iodide transport / regulation of gastric acid secretion / voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization / Phase 3 - rapid repolarisation / regulation of potassium ion transport / membrane repolarization during atrial cardiac muscle cell action potential / membrane repolarization during action potential / telethonin binding / Phase 2 - plateau phase / regulation of atrial cardiac muscle cell membrane repolarization / intracellular chloride ion homeostasis / membrane repolarization during ventricular cardiac muscle cell action potential / membrane repolarization during cardiac muscle cell action potential / negative regulation of delayed rectifier potassium channel activity / potassium ion export across plasma membrane / renal sodium ion absorption / voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization / atrial cardiac muscle cell action potential / membrane repolarization / auditory receptor cell development / regulation of membrane repolarization / protein phosphatase 1 binding / detection of mechanical stimulus involved in sensory perception of sound / delayed rectifier potassium channel activity / ventricular cardiac muscle cell action potential / potassium ion homeostasis / Voltage gated Potassium channels / positive regulation of potassium ion transmembrane transport / regulation of ventricular cardiac muscle cell membrane repolarization / cardiac muscle cell action potential involved in contraction / non-motile cilium assembly / outward rectifier potassium channel activity / cardiac muscle cell contraction / regulation of potassium ion transmembrane transport / epithelial cell maturation / CaM pathway / Cam-PDE 1 activation / intestinal absorption / Sodium/Calcium exchangers / Calmodulin induced events / Reduction of cytosolic Ca++ levels / Activation of Ca-permeable Kainate Receptor / CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde / Loss of phosphorylation of MECP2 at T308 / CREB1 phosphorylation through the activation of Adenylate Cyclase / inner ear morphogenesis / CaMK IV-mediated phosphorylation of CREB / PKA activation / negative regulation of high voltage-gated calcium channel activity / Glycogen breakdown (glycogenolysis) / CLEC7A (Dectin-1) induces NFAT activation / Activation of RAC1 downstream of NMDARs / negative regulation of ryanodine-sensitive calcium-release channel activity / organelle localization by membrane tethering / adrenergic receptor signaling pathway / mitochondrion-endoplasmic reticulum membrane tethering / autophagosome membrane docking / negative regulation of calcium ion export across plasma membrane / regulation of cardiac muscle cell action potential / ciliary base / renal absorption / regulation of heart contraction / presynaptic endocytosis / protein kinase A regulatory subunit binding / Synthesis of IP3 and IP4 in the cytosol / protein kinase A catalytic subunit binding / regulation of cell communication by electrical coupling involved in cardiac conduction / Phase 0 - rapid depolarisation / potassium ion import across plasma membrane / calcineurin-mediated signaling / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / inner ear development / RHO GTPases activate PAKs / regulation of heart rate by cardiac conduction / Ion transport by P-type ATPases / Uptake and function of anthrax toxins / action potential / regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / Long-term potentiation / cochlea development / Calcineurin activates NFAT / Regulation of MECP2 expression and activity / social behavior / DARPP-32 events / voltage-gated potassium channel activity / catalytic complex / Smooth Muscle Contraction
Similarity search - Function
Potassium voltage-gated channel subfamily E member 1 / Potassium channel, voltage-dependent, beta subunit, KCNE / Slow voltage-gated potassium channel / Potassium channel, voltage dependent, KCNQ1 / Potassium channel, voltage dependent, KCNQ / Potassium channel, voltage dependent, KCNQ, C-terminal / KCNQ voltage-gated potassium channel / Voltage-dependent channel domain superfamily / : / EF-hand domain pair ...Potassium voltage-gated channel subfamily E member 1 / Potassium channel, voltage-dependent, beta subunit, KCNE / Slow voltage-gated potassium channel / Potassium channel, voltage dependent, KCNQ1 / Potassium channel, voltage dependent, KCNQ / Potassium channel, voltage dependent, KCNQ, C-terminal / KCNQ voltage-gated potassium channel / Voltage-dependent channel domain superfamily / : / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / Ion transport domain / Ion transport protein / EF-hand domain pair
Similarity search - Domain/homology
: / Chem-PT5 / Calmodulin-1 / Potassium voltage-gated channel subfamily E member 1 / Potassium voltage-gated channel subfamily KQT member 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsHou, P.P. / Zhang, J. / Wan, S.Y. / Cheng, X.Y. / Zhong, L. / Hu, B.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Res / Year: 2025
Title: Secondary structure transitions and dual PIP2 binding define cardiac KCNQ1-KCNE1 channel gating.
Authors: Ling Zhong / Xiaoqing Lin / Xinyu Cheng / Shuangyan Wan / Yaoguang Hua / Weiwei Nan / Bin Hu / Xiangjun Peng / Zihan Zhou / Qiansen Zhang / Huaiyu Yang / Frank Noé / Zhenzhen Yan / Dexiang ...Authors: Ling Zhong / Xiaoqing Lin / Xinyu Cheng / Shuangyan Wan / Yaoguang Hua / Weiwei Nan / Bin Hu / Xiangjun Peng / Zihan Zhou / Qiansen Zhang / Huaiyu Yang / Frank Noé / Zhenzhen Yan / Dexiang Jiang / Hangyu Zhang / Fengjiao Liu / Chenxin Xiao / Zhuo Zhou / Yimin Mou / Haijie Yu / Lijuan Ma / Chen Huang / Vincent Kam Wai Wong / Sookja Kim Chung / Bing Shen / Zhi-Hong Jiang / Erwin Neher / Wandi Zhu / Jin Zhang / Panpan Hou /
Abstract: The KCNQ1 + KCNE1 potassium channel complex produces the slow delayed rectifier current (I) critical for cardiac repolarization. Loss-of-function mutations in KCNQ1 and KCNE1 cause long QT ...The KCNQ1 + KCNE1 potassium channel complex produces the slow delayed rectifier current (I) critical for cardiac repolarization. Loss-of-function mutations in KCNQ1 and KCNE1 cause long QT syndrome (LQTS) types 1 and 5 (LQT1/LQT5), accounting for over one-third of clinical LQTS cases. Despite prior structural work on KCNQ1 and KCNQ1 + KCNE3, the structural basis of KCNQ1 + KCNE1 remains unresolved. Using cryo-electron microscopy and electrophysiology, we determined high-resolution (2.5-3.4 Å) structures of human KCNQ1, and KCNQ1 + KCNE1 in both closed and open states. KCNE1 occupies a pivotal position at the interface of three KCNQ1 subunits, inducing six helix-to-loop transitions in KCNQ1 transmembrane segments. Three of them occur at both ends of the S4-S5 linker, maintaining a loop conformation during I gating, while the other three, in S6 and helix A, undergo dynamic helix-loop transitions during I gating. These structural rearrangements: (1) stabilize the closed pore and the conformation of the intermediate state voltage-sensing domain, thereby determining channel gating, ion permeation, and single-channel conductance; (2) enable a dual-PIP2 modulation mechanism, where one PIP2 occupies the canonical site, while the second PIP2 bridges the S4-S5 linker, KCNE1, and the adjacent S6', stabilizing channel opening; (3) create a fenestration capable of binding compounds specific for KCNQ1 + KCNE1 (e.g., AC-1). Together, these findings reveal a previously unrecognized large-scale secondary structural transition during ion channel gating that fine-tunes I function and provides a foundation for developing targeted LQTS therapy.
History
DepositionMar 24, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Nov 5, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Potassium voltage-gated channel subfamily KQT member 1
B: Calmodulin-1
C: Potassium voltage-gated channel subfamily E member 1
D: Potassium voltage-gated channel subfamily KQT member 1
E: Calmodulin-1
F: Potassium voltage-gated channel subfamily E member 1
G: Potassium voltage-gated channel subfamily KQT member 1
H: Calmodulin-1
I: Potassium voltage-gated channel subfamily E member 1
J: Potassium voltage-gated channel subfamily KQT member 1
K: Calmodulin-1
L: Potassium voltage-gated channel subfamily E member 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)430,04028
Polymers425,37512
Non-polymers4,66516
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Potassium voltage-gated channel subfamily ... , 2 types, 8 molecules ADGJCFIL

#1: Protein
Potassium voltage-gated channel subfamily KQT member 1 / IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1 / KQT-like 1 / Voltage- ...IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1 / KQT-like 1 / Voltage-gated potassium channel subunit Kv7.1


Mass: 74800.492 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KCNQ1, KCNA8, KCNA9, KVLQT1 / Production host: Homo sapiens (human) / References: UniProt: P51787
#3: Protein
Potassium voltage-gated channel subfamily E member 1 / Delayed rectifier potassium channel subunit IsK / IKs producing slow voltage-gated potassium ...Delayed rectifier potassium channel subunit IsK / IKs producing slow voltage-gated potassium channel subunit beta Mink / Minimal potassium channel / MinK


Mass: 14690.725 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KCNE1 / Production host: Homo sapiens (human) / References: UniProt: P15382

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Protein , 1 types, 4 molecules BEHK

#2: Protein
Calmodulin-1


Mass: 16852.545 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CALM1, CALM, CAM, CAM1 / Production host: Homo sapiens (human) / References: UniProt: P0DP23

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Non-polymers , 3 types, 16 molecules

#4: Chemical
ChemComp-PT5 / [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho ryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate / Phosphatidylinositol 4,5-bisphosphate / PtdIns(4,5)P2


Mass: 1047.088 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C47H85O19P3 / Feature type: SUBJECT OF INVESTIGATION / Comment: phospholipid*YM
#5: Chemical
ChemComp-K / POTASSIUM ION


Mass: 39.098 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: K / Feature type: SUBJECT OF INVESTIGATION
#6: Chemical
ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION

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Details

Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Structure of human KCNQ1-KCNE1-CaM complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company
MicroscopyModel: FEI TECNAI SPIRIT
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 51.45 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k)

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Processing

EM software
IDNameCategory
1cryoSPARCparticle selection
4cryoSPARCCTF correction
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 152699 / Symmetry type: POINT

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