7vih
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7vih]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VIH FirstGlance]. <br> | <table><tr><td colspan='2'>[[7vih]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VIH FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7I4:1-[[2-fluoranyl-4-[5-[4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic+acid'>7I4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.98Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7I4:1-[[2-fluoranyl-4-[5-[4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]azetidine-3-carboxylic+acid'>7I4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7vih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vih OCA], [https://pdbe.org/7vih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vih RCSB], [https://www.ebi.ac.uk/pdbsum/7vih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vih ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7vih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vih OCA], [https://pdbe.org/7vih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vih RCSB], [https://www.ebi.ac.uk/pdbsum/7vih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vih ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref> | |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | As a critical sphingolipid metabolite, sphingosine-1-phosphate (S1P) plays an essential role in immune and vascular systems. There are five S1P receptors, designated as S1PR1 to S1PR5, encoded in the human genome, and their activities are governed by endogenous S1P, lipid-like S1P mimics, or nonlipid-like therapeutic molecules. Among S1PRs, S1PR1 stands out due to its nonredundant functions, such as the egress of T and B cells from the thymus and secondary lymphoid tissues, making it a potential therapeutic target. However, the structural basis of S1PR1 activation and regulation by various agonists remains unclear. Here, we report four atomic resolution cryo-electron microscopy (cryo-EM) structures of Gi-coupled human S1PR1 complexes: bound to endogenous agonist d18:1 S1P, benchmark lipid-like S1P mimic phosphorylated Fingolimod [(S)-FTY720-P], or nonlipid-like therapeutic molecule CBP-307 in two binding modes. Our results revealed the similarities and differences of activation of S1PR1 through distinct ligands binding to the amphiphilic orthosteric pocket. We also proposed a two-step "shallow to deep" transition process of CBP-307 for S1PR1 activation. Both binding modes of CBP-307 could activate S1PR1, but from shallow to deep transition may trigger the rotation of the N-terminal helix of Galphai and further stabilize the complex by increasing the Galphai interaction with the cell membrane. We combine with extensive biochemical analysis and molecular dynamic simulations to suggest key steps of S1P binding and receptor activation. The above results decipher the common feature of the S1PR1 agonist recognition and activation mechanism and will firmly promote the development of therapeutics targeting S1PRs. | ||
| + | |||
| + | Structural insights into sphingosine-1-phosphate receptor activation.,Yu L, He L, Gan B, Ti R, Xiao Q, Hu H, Zhu L, Wang S, Ren R Proc Natl Acad Sci U S A. 2022 Apr 19;119(16):e2117716119. doi: , 10.1073/pnas.2117716119. Epub 2022 Apr 11. PMID:35412894<ref>PMID:35412894</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7vih" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Transducin 3D structures|Transducin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Cryo-EM structure of Gi coupled Sphingosine 1-phosphate receptor bound with CBP-307
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Categories: Homo sapiens | Large Structures | Mus musculus | Gan B | Ren RB | Xiao QJ | Yu LY
