View source for 2dco


==S1P4 First Extracellular Loop Peptidomimetic==
<StructureSection load='2dco' size='340' side='right'caption='[[2dco]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2dco]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DCO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</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=2dco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dco OCA], [https://pdbe.org/2dco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dco RCSB], [https://www.ebi.ac.uk/pdbsum/2dco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dco ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S1PR4_HUMAN S1PR4_HUMAN] Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes.<ref>PMID:10679247</ref> <ref>PMID:10753843</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
G protein-coupled receptors (GPCRs) control fundamental aspects of human physiology and behaviors. Knowledge of their structures, especially for the loop regions, is limited and has principally been obtained from homology models, mutagenesis data, low resolution structural studies, and high resolution studies of peptide models of receptor segments. We developed an alternate methodology for structurally characterizing GPCR loops, using the human S1P(4) first extracellular loop (E1) as a model system. This methodology uses computational peptide designs based on transmembrane domain (TM) model structures in combination with CD and NMR spectroscopy. The characterized peptides contain segments that mimic the self-assembling extracellular ends of TM 2 and TM 3 separated by E1, including residues R3.28(121) and E3.29(122) that are required for sphingosine 1-phosphate (S1P) binding and receptor activation in the S1P(4) receptor. The S1P(4) loop mimetic peptide interacted specifically with an S1P headgroup analog, O-phosphoethanolamine (PEA), as evidenced by PEA-induced perturbation of disulfide cross-linked coiled-coil first extracellular loop mimetic (CCE1a) (1)H and (15)N backbone amide chemical shifts. CCE1a was capable of weakly binding PEA near biologically relevant residues R29 and E30, which correspond to R3.28 and E3.29 in the full-length S1P(4) receptor, confirming that it has adopted a biologically relevant conformation. We propose that the combination of coiled-coil TM replacement and conformational stabilization with an interhelical disulfide bond is a general design strategy that promotes native-like structure for loops derived from GPCRs.

Peptide design and structural characterization of a GPCR loop mimetic.,Pham TC, Kriwacki RW, Parrill AL Biopolymers. 2007 Jul;86(4):298-310. PMID:17443712<ref>PMID:17443712</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2dco" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kriwacki RW]]
[[Category: Parrill AL]]
[[Category: Pham TCT]]