9s9u

Structure of the human ADGRG1 GAIN domain with engineered disulfides

spinqualitylabelsall models 9s9u, resolution 1.92Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9s9u is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.92Å Ligands: BMA, EPE, GOL, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease AGRG1_HUMAN Bilateral frontoparietal polymicrogyria;Bilateral perisylvian polymicrogyria. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Homozygous deletion of 1 of 2 tandem 15-bp repeats located 144 bp upstream of the ADGRG1 non-coding exon 1m transcription start site, results in impaired perisylvian ADGRG1 expression and disruption of perisylvian gyri (PubMed:24531968). Function AGRG1_HUMAN Adhesion G protein-coupled receptor (aGPCR) for steroid hormone 17alpha-hydroxypregnenolone (17-OH), which is involved in cell adhesion and cell-cell interactions (PubMed:39389061). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as RhoA pathway (PubMed:28874577, PubMed:35418682, PubMed:39389061). ADGRG1 is coupled to G(12) and/or G(13) G proteins (GNA12 and GNA13, respectively) and mediates the activation Rho small GTPases (PubMed:22238662, PubMed:28424266, PubMed:35418682, PubMed:39389061). Acts as a potent suppressor of ferroptosis: binding to 17-OH-binding initiates signaling that down-regulates CD36 and alleviates ferroptosis-induced liver injury (By similarity). Ligand-binding also induces cell adhesion activity via association with proteins such as collagen III/COL3A1 and TGM2 (By similarity). Mediates cell matrix adhesion in developing neurons and hematopoietic stem cells (By similarity). Involved in cortical development, specifically in maintenance of the pial basement membrane integrity and in cortical lamination: association with COL3A1 in the developing brain inhibits neuronal migration via activation of the RhoA pathway (PubMed:24531968). Together with TGM2, acts as a regulator of myelination and myelin repair in oligodendrocyte precursor cells (By similarity). Acts as a hemostatic sensor of shear force: G protein-coupled receptor signaling is activated in response to shear force in platelets, promoting G(13) G protein signaling, and platelet shape change and aggregation in a COL3A1-dependent manner (PubMed:33097663). Acts as an inhibitor of VEGFA production thereby inhibiting angiogenesis through a signaling pathway mediated by PRKCA (PubMed:16757564, PubMed:19572147, PubMed:21724588). Plays a role in the maintenance of hematopoietic stem cells in bone marrow niche (By similarity). Plays an essential role in testis development (By similarity).[UniProtKB:Q8K209] Adhesion G protein-coupled receptor (aGPCR) for phosphatidylserine, which is involved in microglia-mediated synapse pruning during development (By similarity). Required to maintain appropriate synaptic numbers in several brain regions in a time- and circuit-dependent fashion: phosphatidylserine-binding acts as a 'eat-me' signal for apoptotic cells, leading to microglial engulfment of phosphatidylserine-positive synapses (By similarity).[UniProtKB:Q8K209]

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