[English] 日本語
Yorodumi
- EMDB-24466: Cryo-EM structure of Xenopus Patched-1 in complex with GAS1 and S... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-24466
TitleCryo-EM structure of Xenopus Patched-1 in complex with GAS1 and Sonic Hedgehog
Map data
Sample
  • Complex: Patched Hedgehog GAS1 complex
    • Protein or peptide: Patched-1
    • Protein or peptide: Growth arrest-specific protein 1
  • Protein or peptide: Sonic hedgehog protein N-product
  • Ligand: CHOLESTEROL
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: ZINC ION
  • Ligand: CALCIUM ION
  • Ligand: PALMITIC ACID
KeywordsGPCR / complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


regulation of nodal signaling pathway / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation ...regulation of nodal signaling pathway / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of kidney smooth muscle cell differentiation / morphogen activity / regulation of odontogenesis / positive regulation of mesenchymal cell proliferation involved in ureter development / hedgehog receptor activity / trunk neural crest cell migration / Formation of lateral plate mesoderm / hindgut morphogenesis / polarity specification of anterior/posterior axis / negative regulation of alpha-beta T cell differentiation / regulation of prostatic bud formation / formation of anatomical boundary / smoothened binding / positive regulation of striated muscle cell differentiation / regulation of glial cell proliferation / metanephric mesenchymal cell proliferation involved in metanephros development / ventral midline development / trachea morphogenesis / hedgehog family protein binding / cholesterol-protein transferase activity / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / bud outgrowth involved in lung branching / epithelial-mesenchymal cell signaling / Ligand-receptor interactions / lung epithelium development / laminin-1 binding / salivary gland cavitation / negative regulation of cholesterol efflux / spinal cord dorsal/ventral patterning / negative regulation of mesenchymal cell apoptotic process / determination of left/right asymmetry in lateral mesoderm / regulation of ER to Golgi vesicle-mediated transport / cell development / spinal cord motor neuron differentiation / negative regulation of T cell differentiation in thymus / positive regulation of T cell differentiation in thymus / establishment of epithelial cell polarity / skeletal muscle cell proliferation / prostate gland development / intermediate filament organization / limb bud formation / embryonic skeletal system development / stem cell development / skeletal muscle fiber differentiation / positive regulation of cerebellar granule cell precursor proliferation / mesenchymal cell apoptotic process / animal organ formation / Activation of SMO / patched binding / hindbrain development / embryonic digestive tract morphogenesis / positive regulation of skeletal muscle tissue development / somite development / ectoderm development / embryonic foregut morphogenesis / negative regulation of dopaminergic neuron differentiation / epithelial cell proliferation involved in salivary gland morphogenesis / mesenchymal cell proliferation involved in lung development / neuron fate commitment / cerebellar granule cell precursor proliferation / self proteolysis / positive regulation of immature T cell proliferation in thymus / lung lobe morphogenesis / smooth muscle tissue development / dorsal/ventral neural tube patterning / artery development / lymphoid progenitor cell differentiation / positive regulation of astrocyte differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative thymic T cell selection / regulation of stem cell proliferation / pattern specification process / positive regulation of epithelial cell proliferation involved in prostate gland development / male genitalia development / branching involved in salivary gland morphogenesis / Release of Hh-Np from the secreting cell / epithelial cell proliferation involved in prostate gland development / embryonic pattern specification / lung-associated mesenchyme development / intein-mediated protein splicing / glycosaminoglycan binding / oxysterol binding / thalamus development / Formation of axial mesoderm / dopaminergic neuron differentiation / metanephros development / Developmental Lineage of Pancreatic Acinar Cells
Similarity search - Function
Growth arrest-specific protein 1 / GDNF/GAS1 / GDNF/GAS1 domain / GDNF/GAS1 domain / Transmembrane receptor, patched / Hedgehog, N-terminal signalling domain / Hedgehog protein / Hedgehog protein, Hint domain / : / Hint module ...Growth arrest-specific protein 1 / GDNF/GAS1 / GDNF/GAS1 domain / GDNF/GAS1 domain / Transmembrane receptor, patched / Hedgehog, N-terminal signalling domain / Hedgehog protein / Hedgehog protein, Hint domain / : / Hint module / Hedgehog amino-terminal signalling domain / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / : / Sterol-sensing domain of SREBP cleavage-activation / Sterol-sensing domain (SSD) profile. / Hint domain C-terminal / Hint (Hedgehog/Intein) domain C-terminal region / Sterol-sensing domain / Intein N-terminal splicing region / Intein N-terminal splicing motif profile. / Hint domain N-terminal / Hint (Hedgehog/Intein) domain N-terminal region / Hint domain superfamily
Similarity search - Domain/homology
Growth arrest-specific protein 1 / Sonic hedgehog protein / Patched 1 S homeolog
Similarity search - Component
Biological speciesHomo sapiens (human) / Xenopus laevis (African clawed frog)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.53 Å
AuthorsHuang P / Lian T / Wierbowski B / Garcia-Linares S / Jiang J / Salic A
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM122920 United States
CitationJournal: Dev Cell / Year: 2022
Title: Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.
Authors: Pengxiang Huang / Bradley M Wierbowski / Tengfei Lian / Charlene Chan / Sara García-Linares / Jiansen Jiang / Adrian Salic /
Abstract: The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and ...The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and cancer. SHH engagement with PTCH1 requires the GAS1 coreceptor, but the mechanism is unknown. We demonstrate a unique role for GAS1, catalyzing SHH-PTCH1 complex assembly in vertebrate cells by direct SHH transfer from the extracellular SCUBE2 carrier to PTCH1. Structure of the GAS1-SHH-PTCH1 transition state identifies how GAS1 recognizes the SHH palmitate and cholesterol modifications in modular fashion and how it facilitates lipid-dependent SHH handoff to PTCH1. Structure-guided experiments elucidate SHH movement from SCUBE2 to PTCH1, explain disease mutations, and demonstrate that SHH-induced PTCH1 dimerization causes its internalization from the cell surface. These results define how the signaling-competent SHH-PTCH1 complex assembles, the key step triggering the Hedgehog pathway, and provide a paradigm for understanding morphogen reception and its regulation.
History
DepositionJul 18, 2021-
Header (metadata) releaseMar 2, 2022-
Map releaseMar 2, 2022-
UpdateOct 23, 2024-
Current statusOct 23, 2024Processing site: RCSB / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7rhq
  • Surface level: 0.03
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_24466.png

Downloads & links

-
Map

FileDownload / File: emd_24466.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 240 pix.
= 254.4 Å		1.06 Å/pix.
x 240 pix.
= 254.4 Å		1.06 Å/pix.
x 240 pix.
= 254.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.06 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.03 / Movie #1: 0.03
Minimum - Maximum-0.22365619 - 0.35638633
Average (Standard dev.)0.00000689173 (±0.0065497756)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 254.4 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.061.061.06
M x/y/z240240240
origin x/y/z0.0000.0000.000
length x/y/z254.400254.400254.400
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ450450450
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS240240240
D min/max/mean-0.2240.3560.000

-
Supplemental data

-
Sample components

+
Entire : Patched Hedgehog GAS1 complex

EntireName: Patched Hedgehog GAS1 complex
Components
  • Complex: Patched Hedgehog GAS1 complex
    • Protein or peptide: Patched-1
    • Protein or peptide: Growth arrest-specific protein 1
  • Protein or peptide: Sonic hedgehog protein N-product
  • Ligand: CHOLESTEROL
  • Ligand: CHOLESTEROL HEMISUCCINATE
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: ZINC ION
  • Ligand: CALCIUM ION
  • Ligand: PALMITIC ACID

+
Supramolecule #1: Patched Hedgehog GAS1 complex

SupramoleculeName: Patched Hedgehog GAS1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1, #3
Source (natural)Organism: Homo sapiens (human)

+
Macromolecule #1: Patched-1

MacromoleculeName: Patched-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Xenopus laevis (African clawed frog)
Molecular weightTheoretical: 134.622391 KDa
Recombinant expressionOrganism: Insecta environmental sample (insect)
SequenceString: MASAACAAEL GASGEAAAQP RVVRRRGRSR RVAPPDHDYL QRPSYCDANF ALQQISEGKA IGRKAPLWLR AFFQRQLFKL GCYIQKNCG KFLVVGLLIF GAFAVGLRAA NLETNVEELW VEVGGRVSRE LDYTRQKIGE EAMFNPQLMI QTPLEDGANV L TTEALLQH ...String:
MASAACAAEL GASGEAAAQP RVVRRRGRSR RVAPPDHDYL QRPSYCDANF ALQQISEGKA IGRKAPLWLR AFFQRQLFKL GCYIQKNCG KFLVVGLLIF GAFAVGLRAA NLETNVEELW VEVGGRVSRE LDYTRQKIGE EAMFNPQLMI QTPLEDGANV L TTEALLQH LHSALEATKV QVYMYNKPWK LEELCFKSGE LITEAVYVSQ IIDSMYPCLI ITPLDCFWEG AKLQSGMAYL PG KDILQWT NFDPLELLEE LKKGKLHIDI WEEMINKAEV GHGYMDRPCL NPSDKNCPYT APNKNSTKPV DVSLILSGGC YGL SKKYMH WQEELIIGGT VKNASGQIVS ALALQTMFQL MTPKQMYEHF KGHEVVSHMN WNEDKAAAIL EAWQRTYVQV VHQS VPQNS SQKVLPFTTT TLDDILKSFS DVSVIRVASG YLLMLAYACL TMLRWDCAKS QGAVGLAGVL LVALSVAAGL GLCSL IGIS FNAATTQVLP FLALGVGVDD VFLLAHAFSE TGQNKRIPFE DRTGECLKRT GASVALTSIS NVTAFFMAAL IPIPAL RAF SLQAAVVVVF NFAMVLLIFP AILSMDLYRR EVRRLDIFCC FSSPCVSRVI QIEPQAYTDN NDNTRYSLPP TYSSHSF AH ETQITMQSTV QLRTEYDPRT QLYYTTAQPR SEISVQPAAS TPQDVSGQTP ESTSSTRDLI SQFSVHGGSM QCTPDSKW T LSSFAEKHYA PFLLKPKTKV AVILGFLALL SVSLYGTTRV RDGLDLTDIV PRETREYDFI ATQFKYFSFY HMYVVTQKA DYPRAQRLLY ELHKSFVGVR YVLLEGNKQL PKMWLHYFRD WLQGLQDTFD HEWEAGKITR NDYRNASDDA VLAYKLLIQT GNSDKPINL NQLTKQRLVD ADGIIQPNAF YIYLTAWVSN DPVAYAASQA NIRPHPPEWL HDKADDRPET RTIRAAEPIE Y VQFPFYLN GLRETSDFVE AIEKVRAICN NYTSLGVSSY PNGYPFLFWE QYISLRHWLL LSISVVLACT FLVCALFLLN PW TAGIIVM VLALMTVELF GMMGLIGIKL SAVPVVILIA SVGIGVEFTV HVALAFLTAV GDKNRRAVLA LEHMFAPVLD GAV STLLGV LMLAGSEFDF IVRYFFAVLA ILTLLGVLNG LVLLPVLLSF FGPYPEVSPT NGSSSPAAAH HHHHHHHEDQ VDPR LIDGK

UniProtKB: Patched 1 S homeolog

+
Macromolecule #2: Sonic hedgehog protein N-product

MacromoleculeName: Sonic hedgehog protein N-product / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 21.378926 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: CGPGRGFGKR RHPKKLTPLA YKQFIPNVAE KTLGASGRYE GKISRNSERF KELTPNYNPD IIFKDEENTG ADRLMTQRCK DKLNALAIS VMNQWPGVKL RVTEGWDEGG TEDQVDPRLI DGKSGGDGHH SEESLHYEGR AVDITTSDRD RSKYGMLARL A VEAGFDWV ...String:
CGPGRGFGKR RHPKKLTPLA YKQFIPNVAE KTLGASGRYE GKISRNSERF KELTPNYNPD IIFKDEENTG ADRLMTQRCK DKLNALAIS VMNQWPGVKL RVTEGWDEGG TEDQVDPRLI DGKSGGDGHH SEESLHYEGR AVDITTSDRD RSKYGMLARL A VEAGFDWV YYESKAHIHC SVKAENSVAA KSGG

UniProtKB: Sonic hedgehog protein

+
Macromolecule #3: Growth arrest-specific protein 1

MacromoleculeName: Growth arrest-specific protein 1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 29.546764 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GPGSLAHGRR LICWQALLQC QGEPECSYAY NQYAEACAPV LAQHGGGDAP GAAAAAFPAS AASFSSRWRC PSHCISALIQ LNHTRRGPA LEDCDCAQDE NCKSTKRAIE PCLPRTSGGG AGGPGAGGVM GCTEARRRCD RDSRCNLALS RYLTYCGKVF N GLRCTDEC ...String:
GPGSLAHGRR LICWQALLQC QGEPECSYAY NQYAEACAPV LAQHGGGDAP GAAAAAFPAS AASFSSRWRC PSHCISALIQ LNHTRRGPA LEDCDCAQDE NCKSTKRAIE PCLPRTSGGG AGGPGAGGVM GCTEARRRCD RDSRCNLALS RYLTYCGKVF N GLRCTDEC RTVIEDMLAM PKAALLNDCV CDGLERPICE SVKENMARLC FGAELGNGPG SSGSDGGLDD YYDEDYDDEQ RT GGAGGEQ PLDDDDGVPH PPRPGSGAAA SGGRGDLPYG PGRRS

UniProtKB: Growth arrest-specific protein 1

+
Macromolecule #5: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 5 / Number of copies: 2 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

+
Macromolecule #6: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 6 / Number of copies: 1 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

+
Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 2 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

+
Macromolecule #8: ZINC ION

MacromoleculeName: ZINC ION / type: ligand / ID: 8 / Number of copies: 1 / Formula: ZN
Molecular weightTheoretical: 65.409 Da

+
Macromolecule #9: CALCIUM ION

MacromoleculeName: CALCIUM ION / type: ligand / ID: 9 / Number of copies: 2 / Formula: CA
Molecular weightTheoretical: 40.078 Da

+
Macromolecule #10: PALMITIC ACID

MacromoleculeName: PALMITIC ACID / type: ligand / ID: 10 / Number of copies: 1 / Formula: PLM
Molecular weightTheoretical: 256.424 Da
Chemical component information

ChemComp-PLM:
PALMITIC ACID

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 71.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.53 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 54175
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more