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-π 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 Å (1 Å=0.1 nm) closer to the end of the non-polar tail than the phosphate recognition site.
Skip Nav Destination
Article navigation
July 2005
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
June 21 2005
Sphingosine 1-phosphate analogue recognition and selectivity at S1P4 within the endothelial differentiation gene family of receptors
Yuichi INAGAKI;
Yuichi INAGAKI
1
*Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan
Search for other works by this author on:
TrucChi T. PHAM;
TrucChi T. PHAM
1
†Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, TN 38152, U.S.A.
Search for other works by this author on:
Yuko FUJIWARA;
Yuko FUJIWARA
‡Department of Physiology, University of Tennessee Health Sciences Center, Memphis, TN 38163, U.S.A.
Search for other works by this author on:
Takayuki KOHNO;
Takayuki KOHNO
*Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan
Search for other works by this author on:
Daniel A. OSBORNE;
Daniel A. OSBORNE
†Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, TN 38152, U.S.A.
Search for other works by this author on:
Yasuyuki IGARASHI;
Yasuyuki IGARASHI
*Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan
Search for other works by this author on:
Gabor TIGYI;
Gabor TIGYI
†Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, TN 38152, U.S.A.
‡Department of Physiology, University of Tennessee Health Sciences Center, Memphis, TN 38163, U.S.A.
Search for other works by this author on:
Abby L. PARRILL
Abby L. PARRILL
2
†Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, TN 38152, U.S.A.
‡Department of Physiology, University of Tennessee Health Sciences Center, Memphis, TN 38163, U.S.A.
2To whom correspondence should be addressed (email aparrill@memphis.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 05 2005
Revision Received:
February 21 2005
Accepted:
February 25 2005
Accepted Manuscript online:
February 25 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (1): 187–195.
Article history
Received:
January 05 2005
Revision Received:
February 21 2005
Accepted:
February 25 2005
Accepted Manuscript online:
February 25 2005
Citation
Yuichi INAGAKI, TrucChi T. PHAM, Yuko FUJIWARA, Takayuki KOHNO, Daniel A. OSBORNE, Yasuyuki IGARASHI, Gabor TIGYI, Abby L. PARRILL; Sphingosine 1-phosphate analogue recognition and selectivity at S1P4 within the endothelial differentiation gene family of receptors. Biochem J 1 July 2005; 389 (1): 187–195. doi: https://doi.org/10.1042/BJ20050046
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.