[English] 日本語
Yorodumi
- PDB-9ozh: Cryo-EM structure of 1:2:1 ROS1/NEL/NICOL holo-complex, conformat... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9ozh
TitleCryo-EM structure of 1:2:1 ROS1/NEL/NICOL holo-complex, conformation 2.
Components
  • NELL2-interacting cell ontogeny regulator 1
  • Protein NEL
  • Tyrosine-protein kinase receptor
KeywordsSIGNALING PROTEIN / ROS1 / NEL
Function / homology
Function and homology information


negative regulation of retinal ganglion cell axon guidance / columnar/cuboidal epithelial cell development / regulation of phosphate transport / transferrin receptor binding / regulation of TOR signaling / commissural neuron axon guidance / fertilization / 3'-UTR-mediated mRNA stabilization / neural crest cell migration / positive regulation of cell division ...negative regulation of retinal ganglion cell axon guidance / columnar/cuboidal epithelial cell development / regulation of phosphate transport / transferrin receptor binding / regulation of TOR signaling / commissural neuron axon guidance / fertilization / 3'-UTR-mediated mRNA stabilization / neural crest cell migration / positive regulation of cell division / regulation of ERK1 and ERK2 cascade / transmembrane receptor protein tyrosine kinase activity / positive regulation of neuron differentiation / cell surface receptor protein tyrosine kinase signaling pathway / protein kinase C binding / mRNA 3'-UTR binding / receptor protein-tyrosine kinase / heparin binding / protein phosphatase binding / spermatogenesis / gene expression / cell population proliferation / signaling receptor complex / negative regulation of gene expression / calcium ion binding / perinuclear region of cytoplasm / cell surface / : / ATP binding / identical protein binding / plasma membrane / cytoplasm
Similarity search - Function
Neuropeptide-like protein / Neuropeptide-like / : / EGF domain / EGF domain / : / Thrombospondin N-terminal -like domains. / Laminin G domain / von Willebrand factor (vWF) type C domain / von Willebrand factor type C domain ...Neuropeptide-like protein / Neuropeptide-like / : / EGF domain / EGF domain / : / Thrombospondin N-terminal -like domains. / Laminin G domain / von Willebrand factor (vWF) type C domain / von Willebrand factor type C domain / VWFC domain signature. / VWFC domain profile. / Laminin G domain / Laminin G domain / von Willebrand factor (vWF) type C domain / VWFC domain / LDLR class B repeat / Low-density lipoprotein-receptor YWTD domain / : / Calcium-binding EGF domain / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Six-bladed beta-propeller, TolB-like / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / Fibronectin type III domain / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 1. / : / EGF-like domain signature 2. / EGF-like domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Concanavalin A-like lectin/glucanase domain superfamily / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Tyrosine-protein kinase receptor / NELL2-interacting cell ontogeny regulator 1 / Protein NEL
Similarity search - Component
Biological speciesGallus gallus (chicken)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å
AuthorsAn, W.D. / Zhang, X.W. / Bai, X.C.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) United States
CitationJournal: Nat Commun / Year: 2026
Title: Structural insights into the activation of the chicken ROS1 receptor by the NEL/NICOL ligand complex.
Authors: Weidong An / Xuewu Zhang / Xiao-Chen Bai /
Abstract: The receptor tyrosine kinase ROS1 plays essential roles in cell growth and sperm maturation, yet its activation mechanism has remained poorly understood. Here, we report high-resolution cryo-electron ...The receptor tyrosine kinase ROS1 plays essential roles in cell growth and sperm maturation, yet its activation mechanism has remained poorly understood. Here, we report high-resolution cryo-electron microscopy (cryo-EM) structures of chicken ROS1 in its ligand-free form, in complex with its ligand NEL, and with the ligand/co-ligand complex NEL/NICOL. Unliganded ROS1 adopts an arc-shaped conformation. The interaction between NEL and ROS1 is mediated by the VWC2 domain of NEL and the β1 domain of ROS1. Binding of NICOL to the coiled-coil domain of NEL stabilizes NEL into a batwing-shaped asymmetric dimer, which can recruit only one ROS1 molecule due to steric hindrance. Structural analyses and biochemical results suggest that the 2:1 NEL/NICOL complexes further oligomerize through LamG-VWC4 domain interactions, facilitating the clustering of multiple ROS1 for its activation. Functional assays confirm that both NICOL and the multimerization of NEL/NICOL complexes are required for robust ROS1 signaling. Our findings establish NICOL as a critical co-ligand for ROS1 and suggest a distinct ligand-driven oligomerization mechanism for ROS1 activation.
History
DepositionJun 5, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 25, 2026Provider: repository / Type: Initial release
Revision 1.0Feb 25, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Feb 25, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Feb 25, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Feb 25, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Feb 25, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Mar 11, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
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.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update
Revision 1.1Mar 11, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
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.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update
Revision 1.2Apr 8, 2026Group: Data collection / Database references / Category: citation / em_admin / Item: _citation.journal_volume / _em_admin.last_update
Revision 1.2Apr 8, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / Category: citation / em_admin / Data content type: EM metadata / EM metadata / Item: _citation.journal_volume / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Protein NEL
C: Protein NEL
A: NELL2-interacting cell ontogeny regulator 1
D: Tyrosine-protein kinase receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)461,39036
Polymers453,4994
Non-polymers7,89132
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Protein NEL / 93 kDa protein


Mass: 91070.969 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Gallus gallus (chicken) / Gene: NEL / Production host: Homo sapiens (human) / References: UniProt: Q90827
#2: Protein NELL2-interacting cell ontogeny regulator 1 / NELL2-interacting cofactor for lumicrine signaling / NICOL


Mass: 10182.000 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NICOL1, C4orf48 / Production host: Homo sapiens (human) / References: UniProt: Q5BLP8
#3: Protein Tyrosine-protein kinase receptor


Mass: 261174.797 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Gallus gallus (chicken) / Gene: ROS1 / Production host: Homo sapiens (human)
References: UniProt: F1NQL9, receptor protein-tyrosine kinase
#4: Polysaccharide
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#5: Sugar...
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 28 / Source method: obtained synthetically / Formula: C8H15NO6 / Feature type: SUBJECT OF INVESTIGATION
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: 1:2:1 complex between chicken ROS1, chicken NEL and human NICOL
Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Source (natural)Organism: Gallus gallus (chicken)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenConc.: 8 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm
Specimen holderSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

EM software
IDNameVersionCategory
1RELIONparticle selection
2SerialEMimage acquisition
4GctfCTF correction
9PHENIX1.21.1_5286model refinement
10RELIONinitial Euler assignment
11RELIONfinal Euler assignment
12RELIONclassification
13RELION3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16841 / Symmetry type: POINT
RefinementHighest resolution: 4.2 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00226693
ELECTRON MICROSCOPYf_angle_d0.56336257
ELECTRON MICROSCOPYf_dihedral_angle_d12.32610259
ELECTRON MICROSCOPYf_chiral_restr0.0434071
ELECTRON MICROSCOPYf_plane_restr0.0044676

+
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