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Open data
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Basic information
Entry | Database: PDB / ID: 6d1w | ||||||
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Title | human PKD2 F604P mutant | ||||||
![]() | Polycystin-2 | ||||||
![]() | TRANSPORT PROTEIN / Ion Channel / TRP channel / PKD2 / PC2 / TRPP2 | ||||||
Function / homology | ![]() detection of nodal flow / metanephric smooth muscle tissue development / metanephric cortex development / metanephric cortical collecting duct development / metanephric distal tubule development / polycystin complex / mesonephric tubule development / mesonephric duct development / : / metanephric part of ureteric bud development ...detection of nodal flow / metanephric smooth muscle tissue development / metanephric cortex development / metanephric cortical collecting duct development / metanephric distal tubule development / polycystin complex / mesonephric tubule development / mesonephric duct development / : / metanephric part of ureteric bud development / determination of liver left/right asymmetry / renal tubule morphogenesis / metanephric ascending thin limb development / HLH domain binding / basal cortex / metanephric mesenchyme development / metanephric S-shaped body morphogenesis / renal artery morphogenesis / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / migrasome / cilium organization / VxPx cargo-targeting to cilium / detection of mechanical stimulus / calcium-induced calcium release activity / regulation of calcium ion import / cation channel complex / muscle alpha-actinin binding / placenta blood vessel development / voltage-gated monoatomic ion channel activity / cellular response to hydrostatic pressure / voltage-gated monoatomic cation channel activity / cellular response to fluid shear stress / cellular response to osmotic stress / non-motile cilium / outward rectifier potassium channel activity / actinin binding / motile cilium / transcription regulator inhibitor activity / aorta development / determination of left/right symmetry / inorganic cation transmembrane transport / neural tube development / protein heterotetramerization / ciliary membrane / voltage-gated sodium channel activity / branching involved in ureteric bud morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / spinal cord development / heart looping / voltage-gated potassium channel activity / potassium channel activity / cytoplasmic side of endoplasmic reticulum membrane / cell surface receptor signaling pathway via JAK-STAT / centrosome duplication / sodium ion transmembrane transport / negative regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated calcium channel activity / embryonic placenta development / monoatomic cation channel activity / release of sequestered calcium ion into cytosol / cellular response to cAMP / potassium ion transmembrane transport / cytoskeletal protein binding / cellular response to calcium ion / basal plasma membrane / ciliary basal body / liver development / establishment of localization in cell / lumenal side of endoplasmic reticulum membrane / calcium ion transmembrane transport / phosphoprotein binding / protein tetramerization / cytoplasmic vesicle membrane / mitotic spindle / Wnt signaling pathway / cilium / intracellular calcium ion homeostasis / cellular response to reactive oxygen species / calcium ion transport / positive regulation of nitric oxide biosynthetic process / cell-cell junction / lamellipodium / heart development / regulation of cell population proliferation / positive regulation of cytosolic calcium ion concentration / ATPase binding / basolateral plasma membrane / protein homotetramerization / transmembrane transporter binding / regulation of cell cycle / negative regulation of cell population proliferation / signaling receptor binding / calcium ion binding / positive regulation of gene expression / endoplasmic reticulum membrane / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular exosome Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.54 Å | ||||||
![]() | Zheng, W. / Yang, X. / Bulkley, D. / Chen, X.Z. / Cao, E. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels. Authors: Wang Zheng / Xiaoyong Yang / Ruikun Hu / Ruiqi Cai / Laura Hofmann / Zhifei Wang / Qiaolin Hu / Xiong Liu / David Bulkley / Yong Yu / Jingfeng Tang / Veit Flockerzi / Ying Cao / Erhu Cao / Xing-Zhen Chen / ![]() ![]() ![]() ![]() Abstract: PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to ...PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2. We find that a PKD2 gain-of-function gate mutant effectively rescues PKD2 knockdown-induced phenotypes in embryonic zebrafish. The structure of a PKD2 activating mutant F604P by cryo-electron microscopy reveals a π- to α-helix transition within the pore-lining helix S6 that leads to repositioning of the gate residue and channel activation. Overall the results identify hydrophobic gates and a gating mechanism of PKD2 and PKD2L1. | ||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 327.3 KB | Display | ![]() |
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PDB format | ![]() | 252.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 1009.5 KB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 61.4 KB | Display | |
Data in CIF | ![]() | 88.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7786MC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 84996.336 Da / Num. of mol.: 4 / Mutation: F604P Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Sugar | ChemComp-NAG / |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: PKD2 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 300 kDa/nm / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Tecnai Polara / Image courtesy: FEI Company |
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Microscopy | Model: FEI POLARA 300 |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.10.1_2155: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 387454 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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