PDBsum entry 5kvm

Cell adhesion

PDB id: 5kvm

Contents

Protein chains

355 a.a.

95 a.a.

Ligands

THR-TYR-PHE-ALA-VAL-LEU-MET-VAL-SER

NAG-NAG-BMA-BMA

NAG-NAG

NAG

GOL

Waters ×24

PDB id:

5kvm

Name:

Cell adhesion

Title:

Extracellular region of mouse gpr56/adgrg1 in complex with fn3 monobody

Structure:

Adhesion g-protein coupled receptor g1. Chain: a. Fragment: n-terminal fragment (unp residues 28-382). Synonym: g-protein coupled receptor 56,serpentine receptor cyt28. Engineered: yes. Adhesion g-protein coupled receptor g1. Chain: b. Fragment: c-terminal fragment (unp residues 383-391). Synonym: g-protein coupled receptor 56,serpentine receptor cyt28.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: adgrg1, cyt28, gpr56. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell: high five. Synthetic construct. Organism_taxid: 32630.

Resolution:

2.45Å R-factor: 0.217 R-free: 0.263

Authors:

G.S.Salzman,C.Ding,S.Koide,D.Arac

Key ref:

G.S.Salzman et al. (2016). Structural Basis for Regulation of GPR56/ADGRG1 by Its Alternatively Spliced Extracellular Domains. Neuron, 91, 1292-1304. PubMed id: 27657451

Date:

14-Jul-16 Release date: 28-Sep-16

Protein chain

Q8K209  (AGRG1_MOUSE) -  Adhesion G-protein coupled receptor G1 from Mus musculus

Seq: 687 a.a.

Struc: 355 a.a.

Protein chain

No UniProt id for this chain

Struc: 95 a.a.

Neuron 91:1292-1304 (2016)

PubMed id: 27657451

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

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

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.