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

Tsugumi Okusawa, Mari Fujita, Jun Ichiro Nakamura, Takeshi Into, Motoaki Yasuda, Atsutoshi Yoshimura, Yoshitaka Hara, Akira Hasebe, Douglas T. Golenbock, Manabu Morita, Yoshio Kuroki, Tomohiko Ogawa, Ken Ichiro Shibata

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

The lipopeptide FSL-1 [S-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro-Lys-Ser-Phe, Pam 2CG DPKHPKSF] 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 Mycoplasmafermentans-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-κB reporter activity of FSL-1 to human embryonic kidney 293 cells transfected with Toll-like receptor 2 and 6, together with a NF-κB-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.

Original languageEnglish
Pages (from-to)1657-1665
Number of pages9
JournalInfection and Immunity
Volume72
Issue number3
DOIs
Publication statusPublished - Mar 2004
Externally publishedYes

Fingerprint

Toll-Like Receptor 6
Lipopeptides
Toll-Like Receptor 2
Peptides
Mycoplasma salivarium
Amino Acid Sequence
Macrophages
Palmitic Acid
Chemokine CCL2
Intercellular Adhesion Molecule-1
Amino Acid Substitution
Luciferases
Interleukin-8
Lipoproteins
Interleukin-6
Plasmids
Fatty Acids
Tumor Necrosis Factor-alpha
Fibroblasts
Kidney

ASJC Scopus subject areas

  • Immunology

Cite this

Relationship between Structures and Biological Activities of Mycoplasmal Diacylated Lipopeptides and Their Recognition by Toll-Like Receptors 2 and 6. / Okusawa, Tsugumi; Fujita, Mari; Nakamura, Jun Ichiro; Into, Takeshi; Yasuda, Motoaki; Yoshimura, Atsutoshi; Hara, Yoshitaka; Hasebe, Akira; Golenbock, Douglas T.; Morita, Manabu; Kuroki, Yoshio; Ogawa, Tomohiko; Shibata, Ken Ichiro.

In: Infection and Immunity, Vol. 72, No. 3, 03.2004, p. 1657-1665.

Research output: Contribution to journalArticle

Okusawa, T, Fujita, M, Nakamura, JI, Into, T, Yasuda, M, Yoshimura, A, Hara, Y, Hasebe, A, Golenbock, DT, Morita, M, Kuroki, Y, Ogawa, T & Shibata, KI 2004, 'Relationship between Structures and Biological Activities of Mycoplasmal Diacylated Lipopeptides and Their Recognition by Toll-Like Receptors 2 and 6', Infection and Immunity, vol. 72, no. 3, pp. 1657-1665. https://doi.org/10.1128/IAI.72.3.1657-1665.2004
Okusawa, Tsugumi ; Fujita, Mari ; Nakamura, Jun Ichiro ; Into, Takeshi ; Yasuda, Motoaki ; Yoshimura, Atsutoshi ; Hara, Yoshitaka ; Hasebe, Akira ; Golenbock, Douglas T. ; Morita, Manabu ; Kuroki, Yoshio ; Ogawa, Tomohiko ; Shibata, Ken Ichiro. / Relationship between Structures and Biological Activities of Mycoplasmal Diacylated Lipopeptides and Their Recognition by Toll-Like Receptors 2 and 6. In: Infection and Immunity. 2004 ; Vol. 72, No. 3. pp. 1657-1665.
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AU - Into, Takeshi

AU - Yasuda, Motoaki

AU - Yoshimura, Atsutoshi

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