Sphingosine 1-phosphate analogue recognition and selectivity at S1P4 within the endothelial differentiation gene family of receptors.
Synergistic computational and experimental studies provided previously unforeseen details concerning the structural basis of S1P (sphingosine 1-phosphate) recognition by the S1P4 G-protein-coupled receptor. Similarly to reports on the S1P1 receptor, cationic and anionic residues in the third transmembrane domain (R3.28 and E3.29 at positions 124 and 125) form ion pairs with the phosphate and ammonium of S1P, and alanine mutations at these positions abolished specific S1P binding, S1P-induced receptor activation and cell migration. Unlike findings on the S1P1 receptor, no cationic residue in the seventh transmembrane domain interacts with the phosphate. Additionally, two previously undiscovered interactions with the S1P polar headgroup have been identified. Trp186 at position 4.64 in the fourth transmembrane domain interacts by a cation-pi interaction with the ammonium group of S1P. Lys204 at position 5.38 forms an ion pair with the S1P. The S1P4 and S1P1 receptors show differences in binding-pocket shape and electrostatic distributions that correlate with the published structure-activity relationships. In particular, the binding pocket of mS1P4 (mouse S1P4) has recognition sites for the anionic phosphate and cationic ammonium groups that are equidistant from the end of the non-polar tail. In contrast, the binding pocket of hS1P1 (human S1P4) places the ammonium recognition site 2 A (1 A=0.1 nm) closer to the end of the non-polar tail than the phosphate recognition site.
Inagaki
Yuichi
Y
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Pham
Trucchi T
TT
Fujiwara
Yuko
Y
Kohno
Takayuki
T
Osborne
Daniel A
DA
Igarashi
Yasuyuki
Y
Tigyi
Gabor
G
Parrill
Abby L
AL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D006224:Cricetinae; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D005810:Multigene Family; D009154:Mutation; D049349:Receptors, Lysosphingolipid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D008024:Ligands; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C117422:phytosphingosine-1-phosphate; C060504:dihydrosphingosine 1-phosphate; C060506:sphingosine 1-phosphate; D013110:Sphingosine
Ann N Y Acad Sci. 2000 Apr;905:330-9
10818477
Bioorg Med Chem Lett. 2004 May 17;14(10):2499-503
15109640
FASEB J. 2004 Jun;18(9):1043-5
15084513
Br J Pharmacol. 2004 Jul;142(5):851-60
15197107
Semin Cell Dev Biol. 2004 Oct;15(5):467-76
15271292
BMC Biochem. 2004 Aug 6;5:12
15298705
Bioorg Med Chem Lett. 2004 Oct 4;14(19):4861-6
15341940
J Mol Biol. 1970 Mar;48(3):443-53
5420325
J Biol Chem. 1994 Nov 11;269(45):27900-6
7961722
Biophys J. 1997 May;72(5):1963-85
9129801
J Immunol. 1998 May 15;160(10):5037-44
9590253
J Cell Biol. 1998 Jul 13;142(1):229-40
9660876
J Biol Chem. 1998 Oct 16;273(42):27104-10
9765227
Genomics. 1998 Oct 15;53(2):164-9
9790765
J Cell Biochem. 2003 Mar 1;88(4):732-43
12577307
Biochem Biophys Res Commun. 2000 Feb 16;268(2):583-9
10679247
Blood. 2000 Apr 15;95(8):2624-9
10753843
J Biol Chem. 2000 Dec 15;275(50):39379-84
10982820
Nucleic Acids Res. 2001 Jan 1;29(1):346-9
11125133
Eur J Pharmacol. 2001 Mar 2;414(2-3):145-54
11239914
Biochemistry. 2001 Nov 20;40(46):14053-60
11705398
J Biol Chem. 2001 Dec 28;276(52):49213-20
11604399
Circ Res. 2002 Feb 22;90(3):325-32
11861422
Anal Biochem. 2002 Apr 15;303(2):167-75
11950216
Science. 2002 Apr 12;296(5566):346-9
11923495
J Biol Chem. 2002 Jun 14;277(24):21453-7
11967257
Biochim Biophys Acta. 2002 May 23;1582(1-3):112-20
12069818
FASEB J. 2002 Jul;16(9):983-92
12087059
Curr Opin Immunol. 2002 Oct;14(5):569-75
12183155
Biochem Biophys Res Commun. 2002 Sep 27;297(3):600-6
12270137
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12622-7
12351677
Biochem Biophys Res Commun. 2002 Dec 6;299(3):483-7
12445827
Bioorg Med Chem Lett. 2003 Jan 20;13(2):237-40
12482430
Annu Rev Physiol. 2003;65:23-43
12471161
Bioorg Med Chem Lett. 2003 Feb 24;13(4):661-4
12639553
Pharmacol Res. 2003 May;47(5):401-7
12676514
J Cell Biochem. 2003 Jun 1;89(3):507-19
12761884
Blood. 2003 Jun 15;101(12):4909-15
12586615
Genes Cells. 2003 Aug;8(8):685-97
12875654
J Biol Chem. 2003 Aug 29;278(35):32841-51
12810709
J Org Chem. 2003 Sep 5;68(18):7046-50
12946147
Biochem J. 2003 Sep 15;374(Pt 3):715-22
12803545
Bioorg Med Chem Lett. 2003 Oct 20;13(20):3401-4
14505636
Biochem Biophys Res Commun. 2003 Nov 14;311(2):329-36
14592418
FEBS Lett. 2003 Nov 20;554(3):443-9
14623109
Biochem Soc Trans. 2003 Dec;31(Pt 6):1216-9
14641029
Nature. 2004 Jan 22;427(6972):355-60
14737169
J Neurochem. 2000 Dec;75(6):2485-91
11080201