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- PDB-7q3e: Structure of the mouse CPLANE-RSG1 complex -

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Basic information

Entry
Database: PDB / ID: 7q3e
TitleStructure of the mouse CPLANE-RSG1 complex
Components
  • Ciliogenesis and planar polarity effector 2
  • Protein fuzzy homolog
  • Protein inturned
  • WD repeat-containing and planar cell polarity effector protein fritz homolog
KeywordsPROTEIN TRANSPORT / ciliogenesis / ciliopathies / longin / lipid binding
Function / homology
Function and homology information


auditory receptor cell morphogenesis / axonemal basal plate / respiratory system development / tongue morphogenesis / regulation of embryonic cell shape / regulation of vesicle fusion / septin cytoskeleton organization / digestive system development / regulation of ruffle assembly / protein localization => GO:0008104 ...auditory receptor cell morphogenesis / axonemal basal plate / respiratory system development / tongue morphogenesis / regulation of embryonic cell shape / regulation of vesicle fusion / septin cytoskeleton organization / digestive system development / regulation of ruffle assembly / protein localization => GO:0008104 / regulation of fibroblast migration / podocyte cell migration / establishment of planar polarity / spinal cord dorsal/ventral patterning / motile cilium assembly / cilium organization / circulatory system development / Hedgehog 'off' state / negative regulation of cell division / positive regulation of cilium assembly / regulation of exocytosis / non-motile cilium assembly / regulation of smoothened signaling pathway / positive regulation of smoothened signaling pathway / camera-type eye development / motile cilium / regulation of establishment of cell polarity / neural tube development / limb development / regulation of focal adhesion assembly / smoothened signaling pathway / embryonic digit morphogenesis / hair follicle morphogenesis / roof of mouth development / exocytosis / axoneme / cilium assembly / regulation of ossification / negative regulation of keratinocyte proliferation / embryonic organ development / vesicle-mediated transport / keratinocyte differentiation / negative regulation of cell migration / ciliary basal body / kidney development / neural tube closure / establishment of protein localization / cilium / regulation of protein localization / protein transport / nervous system development / cytoskeleton / GTPase activity / GTP binding / cell surface / plasma membrane / cytoplasm
Similarity search - Function
Ciliogenesis and planar polarity effector 2 / WD repeat-containing and planar cell polarity effector protein Fritz / Fuzzy protein / Protein inturned / WD repeat-containing and planar cell polarity effector protein Fritz / CCZ1/INTU, second Longin domain / CCZ1/INTU/HPS4, third Longin domain / Intu longin-like domain 2 / Intu longin-like domain 3 / CCZ1/INTU/HSP4, first Longin domain ...Ciliogenesis and planar polarity effector 2 / WD repeat-containing and planar cell polarity effector protein Fritz / Fuzzy protein / Protein inturned / WD repeat-containing and planar cell polarity effector protein Fritz / CCZ1/INTU, second Longin domain / CCZ1/INTU/HPS4, third Longin domain / Intu longin-like domain 2 / Intu longin-like domain 3 / CCZ1/INTU/HSP4, first Longin domain / First Longin domain of INTU, CCZ1 and HPS4 / FUZ/MON1/HPS1, third Longin domain / FUZ/MON1/HPS1, second Longin domain / FUZ/MON1/HPS1, first Longin domain / First Longin domain of FUZ, MON1 and HPS1 / Second Longin domain of FUZ, MON1 and HPS1 / Third Longin domain of FUZ, MON1 and HPS1 / Small GTPase / Ras family / PDZ domain profile. / Domain present in PSD-95, Dlg, and ZO-1/2. / PDZ domain / PDZ superfamily / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
GUANOSINE-5'-TRIPHOSPHATE / Ciliogenesis and planar polarity effector 2 / Protein fuzzy homolog / Protein inturned / WD repeat-containing and planar cell polarity effector protein fritz homolog
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.35 Å
AuthorsLangousis, G. / Cavadini, S. / Kempf, G. / Matthias, P.
Funding support2items
OrganizationGrant numberCountry
Swiss National Science Foundation
Other private
CitationJournal: Sci Adv / Year: 2022
Title: Structure of the ciliogenesis-associated CPLANE complex.
Authors: Gerasimos Langousis / Simone Cavadini / Niels Boegholm / Esben Lorentzen / Georg Kempf / Patrick Matthias /
Abstract: Dysfunctional cilia cause pleiotropic human diseases termed ciliopathies. These hereditary maladies are often caused by defects in cilia assembly, a complex event that is regulated by the ...Dysfunctional cilia cause pleiotropic human diseases termed ciliopathies. These hereditary maladies are often caused by defects in cilia assembly, a complex event that is regulated by the ciliogenesis and planar polarity effector (CPLANE) proteins Wdpcp, Inturned, and Fuzzy. CPLANE proteins are essential for building the cilium and are mutated in multiple ciliopathies, yet their structure and molecular functions remain elusive. Here, we show that mammalian CPLANE proteins comprise a bona fide complex and report the near-atomic resolution structures of the human Wdpcp-Inturned-Fuzzy complex and of the mouse Wdpcp-Inturned-Fuzzy complex bound to the small guanosine triphosphatase Rsg1. Notably, the crescent-shaped CPLANE complex binds phospholipids such as phosphatidylinositol 3-phosphate via multiple modules and a CPLANE ciliopathy mutant exhibits aberrant lipid binding. Our study provides critical structural and functional insights into an enigmatic ciliogenesis-associated complex as well as unexpected molecular rationales for ciliopathies.
History
DepositionOct 27, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 6, 2022Provider: repository / Type: Initial release
Revision 1.1Apr 13, 2022Group: Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year
Revision 1.2Apr 27, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: WD repeat-containing and planar cell polarity effector protein fritz homolog
B: Protein inturned
C: Protein fuzzy homolog
D: Ciliogenesis and planar polarity effector 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)268,1435
Polymers267,6204
Non-polymers5231
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area14130 Å2
ΔGint-61 kcal/mol
Surface area66400 Å2

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Components

#1: Protein WD repeat-containing and planar cell polarity effector protein fritz homolog / mFrtz / Homolog-13 / WD repeat-containing and planar cell polarity effector protein


Mass: 86286.477 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Wdpcp / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8C456
#2: Protein Protein inturned / Inturned planar cell polarity effector homolog / PDZ domain-containing protein 6


Mass: 107330.539 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Intu, Kiaa1284, Pdzd6 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q059U7
#3: Protein Protein fuzzy homolog


Mass: 45542.906 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Fuz / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: E9QL29
#4: Protein Ciliogenesis and planar polarity effector 2 / REM2- and Rab-like small GTPase 1


Mass: 28459.801 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Cplane2, Gm723, Rsg1 / Production host: Escherichia coli (E. coli) / References: UniProt: A2A825
#5: Chemical ChemComp-GTP / GUANOSINE-5'-TRIPHOSPHATE


Mass: 523.180 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H16N5O14P3 / Comment: GTP, energy-carrying molecule*YM
Has ligand of interestN

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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: CPLANE complex / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Source (natural)Organism: Mus musculus (house mouse)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 8
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: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 1.04 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.35 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 94157 / Symmetry type: POINT

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