5KVM

Extracellular region of mouse GPR56/ADGRG1 in complex with FN3 monobody


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.45 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

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This is version 2.0 of the entry. See complete history


Literature

Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains.

Salzman, G.S.Ackerman, S.D.Ding, C.Koide, A.Leon, K.Luo, R.Stoveken, H.M.Fernandez, C.G.Tall, G.G.Piao, X.Monk, K.R.Koide, S.Arac, D.

(2016) Neuron 91: 1292-1304

  • DOI: https://doi.org/10.1016/j.neuron.2016.08.022
  • Primary Citation of Related Structures:  
    5KVM

  • PubMed Abstract: 

    Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology.


  • Organizational Affiliation

    Biophysical Sciences Program, The University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, The University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Adhesion G-protein coupled receptor G1355Mus musculusMutation(s): 0 
Gene Names: Adgrg1Cyt28Gpr56
UniProt
Find proteins for Q8K209 (Mus musculus)
Explore Q8K209 
Go to UniProtKB:  Q8K209
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8K209
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Adhesion G-protein coupled receptor G19Mus musculusMutation(s): 0 
Gene Names: Adgrg1Cyt28Gpr56
UniProt
Find proteins for Q8K209 (Mus musculus)
Explore Q8K209 
Go to UniProtKB:  Q8K209
Entity Groups  
UniProt GroupQ8K209
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
FN3 monobody alpha595synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G40894EI
GlyCosmos:  G40894EI
GlyGen:  G40894EI
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
E
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
F [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.336α = 90
b = 120.336β = 90
c = 72.85γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
CRANK2phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesF30-GM116455
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesU54-GM087519
Brain Research FoundationUnited States--

Revision History  (Full details and data files)

  • Version 1.0: 2016-09-28
    Type: Initial release
  • Version 1.1: 2017-09-27
    Changes: Author supporting evidence, Database references, Derived calculations
  • Version 1.2: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.3: 2019-12-25
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary