+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-7786 | |||||||||
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Title | human PKD2 F604P mutant | |||||||||
Map data | Human PKD2 F604P mutant | |||||||||
Sample |
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Function / homology | Function and homology information 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 / regulation of calcium ion import / cation channel complex / calcium-induced calcium release activity / muscle alpha-actinin binding / placenta blood vessel development / voltage-gated monoatomic ion channel activity / cellular response to hydrostatic pressure / outward rectifier potassium channel activity / voltage-gated monoatomic cation channel activity / non-motile cilium / cellular response to fluid shear stress / cellular response to osmotic stress / voltage-gated sodium channel activity / actinin binding / motile cilium / inorganic cation transmembrane transport / transcription regulator inhibitor activity / determination of left/right symmetry / neural tube development / aorta development / protein heterotetramerization / ciliary membrane / branching involved in ureteric bud morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / spinal cord development / heart looping / cytoplasmic side of endoplasmic reticulum membrane / voltage-gated potassium channel activity / cell surface receptor signaling pathway via JAK-STAT / potassium channel activity / 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 / cellular response to cAMP / release of sequestered calcium ion into cytosol / potassium ion transmembrane transport / cellular response to calcium ion / cytoskeletal protein binding / basal plasma membrane / ciliary basal body / liver development / establishment of localization in cell / lumenal side of endoplasmic reticulum membrane / calcium ion transmembrane transport / protein tetramerization / phosphoprotein binding / cytoplasmic vesicle membrane / cilium / intracellular calcium ion homeostasis / mitotic spindle / Wnt signaling pathway / cellular response to reactive oxygen species / positive regulation of nitric oxide biosynthetic process / calcium ion transport / cell-cell junction / lamellipodium / regulation of cell population proliferation / heart development / ATPase binding / positive regulation of cytosolic calcium ion concentration / protein homotetramerization / basolateral plasma membrane / transmembrane transporter binding / regulation of cell cycle / negative regulation of cell population proliferation / signaling receptor binding / calcium ion binding / endoplasmic reticulum membrane / positive regulation of gene expression / Golgi apparatus / endoplasmic reticulum / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular exosome Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.54 Å | |||||||||
Authors | Zheng W / Yang X / Bulkley D / Chen XZ / Cao E | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Nat Commun / Year: 2018 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
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_7786.map.gz | 3.1 MB | EMDB map data format | |
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Header (meta data) | emd-7786-v30.xml emd-7786.xml | 15.1 KB 15.1 KB | Display Display | EMDB header |
Images | emd_7786.png | 477.7 KB | ||
Others | emd_7786_half_map_1.map.gz emd_7786_half_map_2.map.gz | 17.7 MB 17.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-7786 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7786 | HTTPS FTP |
-Related structure data
Related structure data | 6d1wMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_7786.map.gz / Format: CCP4 / Size: 27 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Human PKD2 F604P mutant | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.2156 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: Human PKD2 F604P mutant
File | emd_7786_half_map_1.map | ||||||||||||
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Annotation | Human PKD2 F604P mutant | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Human PKD2 F604P mutant
File | emd_7786_half_map_2.map | ||||||||||||
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Annotation | Human PKD2 F604P mutant | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : PKD2
Entire | Name: PKD2Polycystin 2 |
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Components |
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-Supramolecule #1: PKD2
Supramolecule | Name: PKD2 / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 300 kDa/nm |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293S |
-Macromolecule #1: Polycystin-2
Macromolecule | Name: Polycystin-2 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 84.996336 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: EIEMQRIRQA AARDPPAGAA ASPSPPLSSC SRQAWSRDNP GFEAEEEEEE VEGEEGGMVV EMDVEWRPGS RRSAASSAVS SVGARSRGL GGYHGAGHPS GRRRRREDQG PPCPSPVGGG DPLHRHLPLE GQPPRVAWAE RLVRGLRGLW GTRLMEESST N REKYLKSV ...String: EIEMQRIRQA AARDPPAGAA ASPSPPLSSC SRQAWSRDNP GFEAEEEEEE VEGEEGGMVV EMDVEWRPGS RRSAASSAVS SVGARSRGL GGYHGAGHPS GRRRRREDQG PPCPSPVGGG DPLHRHLPLE GQPPRVAWAE RLVRGLRGLW GTRLMEESST N REKYLKSV LRELVTYLLF LIVLCILTYG MMSSNVYYYT RMMSQLFLDT PVSKTEKTNF KTLSSMEDFW KFTEGSLLDG LY WKMQPSN QTEADNRSFI FYENLLLGVP RIRQLRVRNG SCSIPQDLRD EIKECYDVYS VSSEDRAPFG PRNGTAWIYT SEK DLNGSS HWGIIATYSG AGYYLDLSRT REETAAQVAS LKKNVWLDRG TRATFIDFSV YNANINLFCV VRLLVEFPAT GGVI PSWQF QPLKLIRYVT TFDFFLAACE IIFCFFIFYY VVEEILEIRI HKLHYFRSFW NCLDVVIVVL SVVAIGINIY RTSNV EVLL QFLEDQNTFP NFEHLAYWQI QFNNIAAVTV FFVWIKLFKF INFNRTMSQL STTMSRCAKD LFGFAIMPFI IFLAYA QLA YLVFGTQVDD FSTFQECIFT QFRIILGDIN FAEIEEANRV LGPIYFTTFV FFMFFILLNM FLAIINDTYS EVKSDLA QQ KAEMELSDLI RKGYHKALVK LKLKKNTVDD ISESLRQGGG KLNFDELRQD LKGKGHTDAE IEAIFTKYDQ DGDQELTE H EHQQMRDDLE KEREDLDLD |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 12 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI POLARA 300 |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2 |
Experimental equipment | Model: Tecnai Polara / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: PROJECTION MATCHING |
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Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 387454 |