[English] 日本語
Yorodumi
- EMDB-72508: BS3-crosslinked Smoothened/PKA-C complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-72508
TitleBS3-crosslinked Smoothened/PKA-C complex
Map data
Sample
  • Complex: BS3-crosslinked Smoothened/PKA-C complex
    • Protein or peptide: mouse Smoothened 64-674
    • Protein or peptide: native-source bovine PKA-C
KeywordsHedgehog signaling / SIGNALING PROTEIN
Function / homology
Function and homology information


regulation of localization / BBSome-mediated cargo-targeting to cilium / ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / response to inositol / regulation of heart morphogenesis / Activation of SMO / contact inhibition / negative regulation of hepatocyte proliferation / negative regulation of hair follicle development ...regulation of localization / BBSome-mediated cargo-targeting to cilium / ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / response to inositol / regulation of heart morphogenesis / Activation of SMO / contact inhibition / negative regulation of hepatocyte proliferation / negative regulation of hair follicle development / 9+0 non-motile cilium / pancreas morphogenesis / negative regulation of DNA binding / epithelial-mesenchymal cell signaling / myoblast migration / atrial septum morphogenesis / axon extension involved in axon guidance / regulation of stem cell population maintenance / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / midgut development / positive regulation of hepatic stellate cell activation / Hedgehog 'on' state / left/right axis specification / CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / cell development / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / RET signaling / AURKA Activation by TPX2 / Interleukin-3, Interleukin-5 and GM-CSF signaling / patched binding / Recruitment of NuMA to mitotic centrosomes / mesenchymal to epithelial transition / VEGFA-VEGFR2 Pathway / somite development / Hedgehog 'off' state / type B pancreatic cell development / PKA activation / forebrain morphogenesis / smooth muscle tissue development / MAPK6/MAPK4 signaling / GLI3 is processed to GLI3R by the proteasome / positive regulation of organ growth / Regulation of PLK1 Activity at G2/M Transition / mammary gland epithelial cell differentiation / positive regulation of branching involved in ureteric bud morphogenesis / Hedgehog 'off' state / cellular response to cholesterol / cerebellar cortex morphogenesis / pattern specification process / dentate gyrus development / oxysterol binding / thalamus development / commissural neuron axon guidance / positive regulation of multicellular organism growth / dorsal/ventral pattern formation / positive regulation of smoothened signaling pathway / central nervous system neuron differentiation / positive regulation of neural precursor cell proliferation / positive regulation of vascular associated smooth muscle cell migration / cAMP-dependent protein kinase inhibitor activity / determination of left/right symmetry / cell fate specification / digestive tract development / anterior/posterior pattern specification / histone H1-4S35 kinase activity / cAMP-dependent protein kinase / positive regulation of mesenchymal cell proliferation / regulation of protein processing / cAMP-dependent protein kinase activity / cellular response to parathyroid hormone stimulus / protein localization to lipid droplet / hair follicle morphogenesis / regulation of bicellular tight junction assembly / cAMP-dependent protein kinase complex / neural crest cell migration / dorsal/ventral neural tube patterning / positive regulation of neuroblast proliferation / ciliary membrane / interleukin-2-mediated signaling pathway / smoothened signaling pathway / Mitochondrial protein degradation / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / regulation of osteoblast differentiation / sperm capacitation / cellular response to cold / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins
Similarity search - Function
Smoothened, transmembrane domain / Smoothened, cysteine-rich domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain ...Smoothened, transmembrane domain / Smoothened, cysteine-rich domain / Frizzled/Smoothened, transmembrane domain / Frizzled/Smoothened family membrane region / Frizzled/Smoothened family membrane region / Frizzled/secreted frizzled-related protein / Frizzled / Frizzled domain / Frizzled cysteine-rich domain superfamily / Fz domain / Frizzled (fz) domain profile. / cAMP-dependent protein kinase catalytic subunit / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
cAMP-dependent protein kinase catalytic subunit alpha / Protein smoothened
Similarity search - Component
Biological speciesMus musculus (house mouse) / Bos taurus (domestic cattle)
Methodsingle particle reconstruction / cryo EM / Resolution: 8.59 Å
AuthorsLiu G / Myers BR
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Eye Institute (NIH/NEI)R01EY035377 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM133672 United States
CitationJournal: Nat Struct Mol Biol / Year: 2026
Title: Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway.
Authors: William P Steiner / Nathan Iverson / Guibing Liu / Varun Venkatakrishnan / Jian Wu / Tomasz Maciej Stepniewski / Zachary Michaelson / Jan W Bröckel / Ju-Fen Zhu / Jessica G H Bruystens / ...Authors: William P Steiner / Nathan Iverson / Guibing Liu / Varun Venkatakrishnan / Jian Wu / Tomasz Maciej Stepniewski / Zachary Michaelson / Jan W Bröckel / Ju-Fen Zhu / Jessica G H Bruystens / Annabel Lee / Isaac Nelson / Daniela Bertinetti / Corvin D Arveseth / Gerald Tan / Paul Spaltenstein / Jiewei Xu / Ruth Hüttenhain / Michael S Kay / Friedrich W Herberg / Erhu Cao / Jana Selent / Ganesh S Anand / Roland L Dunbrack / Susan S Taylor / Benjamin R Myers /
Abstract: The Hedgehog (Hh) pathway is fundamental to embryogenesis, tissue homeostasis and cancer. Hh signals are transduced through an unusual mechanism; upon agonist-induced phosphorylation, the ...The Hedgehog (Hh) pathway is fundamental to embryogenesis, tissue homeostasis and cancer. Hh signals are transduced through an unusual mechanism; upon agonist-induced phosphorylation, the noncanonical G-protein-coupled receptor (GPCR) Smoothened (SMO) binds the protein kinase A (PKA) catalytic subunit (PKA-C) and physically blocks its enzymatic activity. Here, by combining computational structural approaches with biochemical and functional studies, we show that SMO mimics strategies prevalent in canonical GPCR and PKA signaling complexes, despite little sequence or secondary-structure homology. The intrinsically disordered SMO cytoplasmic domain binds the PKA-C active site, resembling the regulatory subunit within PKA holoenzymes, while the SMO transmembrane domain binds a conserved PKA-C interaction hub. Unlike prevailing GPCR signal transduction models, phosphorylation of SMO promotes intramolecular electrostatic interactions that stabilize structural elements within its cytoplasmic domain, thereby remodeling it into a PKA-inhibiting conformation. Our work provides a structural mechanism for a central step in Hh signaling and defines a principle for disordered GPCR domains to transmit signals intracellularly.
History
DepositionSep 4, 2025-
Header (metadata) releaseApr 22, 2026-
Map releaseApr 22, 2026-
UpdateMay 27, 2026-
Current statusMay 27, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_72508.png

Downloads & links

-
Map

FileDownload / File: emd_72508.map.gz / Format: CCP4 / Size: 8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.12 Å/pix.
x 128 pix.
= 271.36 Å		2.12 Å/pix.
x 128 pix.
= 271.36 Å		2.12 Å/pix.
x 128 pix.
= 271.36 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.12 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.1
Minimum - Maximum-0.2279602 - 0.599186
Average (Standard dev.)0.00024070073 (±0.046579488)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions128128128
Spacing128128128
CellA=B=C: 271.36 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_72508_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_72508_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : BS3-crosslinked Smoothened/PKA-C complex

EntireName: BS3-crosslinked Smoothened/PKA-C complex
Components
  • Complex: BS3-crosslinked Smoothened/PKA-C complex
    • Protein or peptide: mouse Smoothened 64-674
    • Protein or peptide: native-source bovine PKA-C

-
Supramolecule #1: BS3-crosslinked Smoothened/PKA-C complex

SupramoleculeName: BS3-crosslinked Smoothened/PKA-C complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Molecular weightTheoretical: 110 KDa

-
Macromolecule #1: mouse Smoothened 64-674

MacromoleculeName: mouse Smoothened 64-674 / type: protein_or_peptide / ID: 1
Details: mouse Smoothened 64-674 with an N-terminal FLAG tag followed by a TEV cleavage site
Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDAGS ENLYFQGSGS PRLLSHCGRA AHCEPLRYNV CLGSALPYGA TTTLLAGDSD SQEEAHGKLV LWSGLRNAPR CWAVIQPLLC AVYMPKCEND RVELPSRTLC QATRGPCAIV ERERGWPDFL RCTPDHFPEG CPNEVQNIKF NSSGQCEAPL VRTDNPKSWY ...String:
DYKDDDDAGS ENLYFQGSGS PRLLSHCGRA AHCEPLRYNV CLGSALPYGA TTTLLAGDSD SQEEAHGKLV LWSGLRNAPR CWAVIQPLLC AVYMPKCEND RVELPSRTLC QATRGPCAIV ERERGWPDFL RCTPDHFPEG CPNEVQNIKF NSSGQCEAPL VRTDNPKSWY EDVEGCGIQC QNPLFTEAEH QDMHSYIAAF GAVTGLCTLF TLATFVADWR NSNRYPAVIL FYVNACFFVG SIGWLAQFMD GARREIVCRA DGTMRFGEPT SSETLSCVII FVIVYYALMA GVVWFVVLTY AWHTSFKALG TTYQPLSGKT SYFHLLTWSL PFVLTVAILA VAQVDGDSVS GICFVGYKNY RYRAGFVLAP IGLVLIVGGY FLIRGVMTLF SIKSNHPGLL SEKAASKINE TMLRLGIFGF LAFGFVLITF SCHFYDFFNQ AEWERSFRDY VLCQANVTIG LPTKKPIPDC EIKNRPSLLV EKINLFAMFG TGIAMSTWVW TKATLLIWRR TWCRLTGHSD DEPKRIKKSK MIAKAFSKRR ELLQNPGQEL SFSMHTVSHD GPVAGLAFDL NEPSADVSSA WAQHVTKMVA RRGAILPQDV SVTPVATPVP PEEQANMWLV EAEISPELEK RLG

UniProtKB: Protein smoothened

-
Macromolecule #2: native-source bovine PKA-C

MacromoleculeName: native-source bovine PKA-C / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO
Source (natural)Organism: Bos taurus (domestic cattle)
SequenceString: GNAAAAKKGS EQESVKEFLA KAKEDFLKKW ENPAQNTAHL DQFERIKTLG TGSFGRVMLV KHMETGNHYA MKILDKQKVV KLKQIEHTLN EKRILQAVNF PFLVKLEFSF KDNSNLYMVM EYVPGGEMFS HLRRIGRFSE PHARFYAAQI VLTFEYLHSL DLIYRDLKPE ...String:
GNAAAAKKGS EQESVKEFLA KAKEDFLKKW ENPAQNTAHL DQFERIKTLG TGSFGRVMLV KHMETGNHYA MKILDKQKVV KLKQIEHTLN EKRILQAVNF PFLVKLEFSF KDNSNLYMVM EYVPGGEMFS HLRRIGRFSE PHARFYAAQI VLTFEYLHSL DLIYRDLKPE NLLIDQQGYI QVTDFGFAKR VKGRTWTLCG TPEYLAPEII LSKGYNKAVD WWALGVLIYE MAAGYPPFFA DQPIQIYEKI VSGKVRFPSH FSSDLKDLLR NLLQVDLTKR FGNLKNGVND IKNHKWFATT DWIAIYQRKV EAPFIPKFKG PGDTSNFDDY EEEEIRVSIN EKCGKEFSEF

UniProtKB: cAMP-dependent protein kinase catalytic subunit alpha

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 8.59 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 21122
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

+
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