IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Okusawa, T.
Right arrow Articles by Shibata, K.-i.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Okusawa, T.
Right arrow Articles by Shibata, K.-i.

 Previous Article  |  Next Article 

Infection and Immunity, March 2004, p. 1657-1665, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1657-1665.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Relationship between Structures and Biological Activities of Mycoplasmal Diacylated Lipopeptides and Their Recognition by Toll-Like Receptors 2 and 6

Tsugumi Okusawa,1 Mari Fujita,1,2 Jun-ichiro Nakamura,1 Takeshi Into,1 Motoaki Yasuda,1 Atsutoshi Yoshimura,3 Yoshitaka Hara,3 Akira Hasebe,1 Douglas T. Golenbock,4 Manabu Morita,2 Yoshio Kuroki,5 Tomohiko Ogawa,6 and Ken-ichiro Shibata1*

Departments of Oral Pathobiological Science,1 Oral Health Science, Hokkaido University Graduate School of Dental Medicine, Nishi 7, Kita 13, Kita-kuSapporo 060-8586,2 Department of Periodontology, Nagasaki University, Graduate School of Biomedical Sciences, Nagasaki 852-8521,3 First Department of Biochemistry, Sapporo Medical University, Sapporo 060-8556,5 Department of Oral Microbiology, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan,6 Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 016054

Received 27 May 2003/ Returned for modification 8 August 2003/ Accepted 13 November 2003

The lipopeptide FSL-1 [S-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro-Lys-Ser-Phe, Pam2CGDPKHPKSF] synthesized on the basis of the N-terminal structure of a Mycoplasma salivarium lipoprotein capable of activating normal human gingival fibroblasts to induce the cell surface expression of ICAM-1 revealed an activity to induce production of monocyte chemoattractant protein 1, interleukin-6 (IL-6), and IL-8. FSL-1 also activated macrophages to produce tumor necrosis factor alpha as the Mycoplasma fermentans-derived lipopeptide MALP-2 (Pam2CGNNDESNISFKEK), a potent macrophage-activating lipopeptide, did. The level of the activity of FSL-1 was higher than that of MALP-2. This result suggests that the difference in the amino acid sequence of the peptide portion affects the activity because the framework structure other than the amino acid sequence of the former is the same as that of the latter. To determine minimal structural requirements for the activity of FSL-1, the diacylglyceryl Cys and the peptide portions were examined for this activity. Both portions did not reveal the activity. A single amino acid substitution from Phe to Arg and a fatty acid substitution from palmitic acid to stearic acid drastically reduced the activity. Similar results were obtained in measuring the NF-{kappa}B reporter activity of FSL-1 to human embryonic kidney 293 cells transfected with Toll-like receptor 2 and 6, together with a NF-{kappa}B-dependent luciferase reporter plasmid. These results suggest that both the diacylglyceryl and the peptide portions of FSL-1 are indispensable for the expression of biological activities and for the recognition by Toll-like receptors 2 and 6 and that the recognition of FSL-1 by Toll-like receptors 2 and 6 appears to be hydrophobic.

* Corresponding author. Mailing address: Ken-ichiro Shibata, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Nishi 7, Kita 13, Kita-ku, Sapporo 060-8586, Japan. Phone: 81-11-706-4240. Fax: 81-11-706-4901. E-mail: shibaken{at}den.hokudai.ac.jp.

Editor: B. B. Finlay

Infection and Immunity, March 2004, p. 1657-1665, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1657-1665.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2004 by the American Society for Microbiology. All rights reserved.