3v2y

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Crystal Structure of a Lipid G protein-Coupled Receptor at 2.80A

Structural highlights

3v2y is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.8Å
Ligands:ML5, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S1PR1_HUMAN G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.[1] [2] [3] [4] [5] [6] [7] [8] ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[9]

Publication Abstract from PubMed

The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.

Crystal structure of a lipid G protein-coupled receptor.,Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC Science. 2012 Feb 17;335(6070):851-5. PMID:22344443[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
120 reviews cite this structure
Sphingolipids and their metabolism in physiology and disease.
Hannun et al. (2018)
119 more
211 other articles
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See Also

References

  1. ↑ Parrill AL, Wang D, Bautista DL, Van Brocklyn JR, Lorincz Z, Fischer DJ, Baker DL, Liliom K, Spiegel S, Tigyi G. Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate. J Biol Chem. 2000 Dec 15;275(50):39379-84. PMID:10982820 doi:http://dx.doi.org/10.1074/jbc.M007680200
  2. ↑ Hobson JP, Rosenfeldt HM, Barak LS, Olivera A, Poulton S, Caron MG, Milstien S, Spiegel S. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science. 2001 Mar 2;291(5509):1800-3. PMID:11230698 doi:http://dx.doi.org/10.1126/science.1057559
  3. ↑ Lee MJ, Thangada S, Paik JH, Sapkota GP, Ancellin N, Chae SS, Wu M, Morales-Ruiz M, Sessa WC, Alessi DR, Hla T. Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Mol Cell. 2001 Sep;8(3):693-704. PMID:11583630
  4. ↑ Wang DA, Lorincz Z, Bautista DL, Liliom K, Tigyi G, Parrill AL. A single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors. J Biol Chem. 2001 Dec 28;276(52):49213-20. Epub 2001 Oct 16. PMID:11604399 doi:http://dx.doi.org/10.1074/jbc.M107301200
  5. ↑ Singleton PA, Chatchavalvanich S, Fu P, Xing J, Birukova AA, Fortune JA, Klibanov AM, Garcia JG, Birukov KG. Akt-mediated transactivation of the S1P1 receptor in caveolin-enriched microdomains regulates endothelial barrier enhancement by oxidized phospholipids. Circ Res. 2009 Apr 24;104(8):978-86. doi: 10.1161/CIRCRESAHA.108.193367. Epub, 2009 Mar 12. PMID:19286607 doi:http://dx.doi.org/10.1161/CIRCRESAHA.108.193367
  6. ↑ Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC. Crystal structure of a lipid G protein-coupled receptor. Science. 2012 Feb 17;335(6070):851-5. PMID:22344443 doi:10.1126/science.1215904
  7. ↑ Lee MJ, Evans M, Hla T. The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. J Biol Chem. 1996 May 10;271(19):11272-9. PMID:8626678
  8. ↑ Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, Spiegel S, Hla T. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science. 1998 Mar 6;279(5356):1552-5. PMID:9488656
  9. ↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:http://dx.doi.org/10.1002/pro.2042
  10. ↑ Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC. Crystal structure of a lipid G protein-coupled receptor. Science. 2012 Feb 17;335(6070):851-5. PMID:22344443 doi:10.1126/science.1215904

Contents


PDB ID 3v2y

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