Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor

Yoshinori Fujimura, Mami Sumida, Kaori Sugihara, Shuntaro Tsukamoto, Koji Yamada, Hirofumi Tachibana

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: We previously identified the 67-kDa laminin receptor (67LR) as the cell-surface receptor conferring the major green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) responsiveness to cancer cells. However, the underlying mechanism for interaction between EGCG and 67LR remains unclear. In this study, we investigated the possible role of EGCG-67LR interaction responsible for its bioactivities. Methodology/Principal Findings: We synthesized various peptides deduced from the extracellular domain corresponding to the 102-295 region of human 67LR encoding a 295-amino acid. The neutralizing activity of these peptides toward EGCG cell-surface binding and inhibition of cancer cell growth were assayed. Both activities were inhibited by a peptide containing the 10-amino acid residues, IPCNNKGAHS, corresponding to residues 161-170. Furthermore, mass spectrometric analysis revealed the formation of a EGCG-LR161-170 peptide complex. A study of the amino acid deletion/replacement of the peptide LR161-170 indicated that the 10-amino acid length and two basic amino acids, K166 and H169, have a critical role in neutralizing EGCG's activities. Moreover, neutralizing activity against the anti-proliferation action of EGCG was observed in a recombinant protein of the extracellular domain of 67LR, and this effect was abrogated by a deletion of residues 161-170. These findings support that the 10 amino-acid sequence, IPCNNKGAHS, might be the functional domain responsible for the anti-cancer activity of EGCG. Conclusions/Significance: Overall, our results highlight the nature of the EGCG-67LR interaction and provide novel structural insights into the understanding of 67LR-mediated functions of EGCG, and could aid in the development of potential anti-cancer compounds for chemopreventive or therapeutic uses that can mimic EGCG-67LR interactions.

Original languageEnglish
Article numbere37942
JournalPloS one
Volume7
Issue number5
DOIs
Publication statusPublished - May 29 2012

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Laminin Receptors
laminin
epigallocatechin
Polyphenols
green tea
Tea
polyphenols
receptors
peptides
Amino Acids
Peptides
neutralization
amino acids
Neoplasms
epigallocatechin gallate
amino acid deletion
development aid
Basic Amino Acids
neoplasms
Cell Surface Receptors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Fujimura, Y., Sumida, M., Sugihara, K., Tsukamoto, S., Yamada, K., & Tachibana, H. (2012). Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor. PloS one, 7(5), [e37942]. https://doi.org/10.1371/journal.pone.0037942

Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor. / Fujimura, Yoshinori; Sumida, Mami; Sugihara, Kaori; Tsukamoto, Shuntaro; Yamada, Koji; Tachibana, Hirofumi.

In: PloS one, Vol. 7, No. 5, e37942, 29.05.2012.

Research output: Contribution to journalArticle

Fujimura, Y, Sumida, M, Sugihara, K, Tsukamoto, S, Yamada, K & Tachibana, H 2012, 'Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor', PloS one, vol. 7, no. 5, e37942. https://doi.org/10.1371/journal.pone.0037942
Fujimura, Yoshinori ; Sumida, Mami ; Sugihara, Kaori ; Tsukamoto, Shuntaro ; Yamada, Koji ; Tachibana, Hirofumi. / Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor. In: PloS one. 2012 ; Vol. 7, No. 5.
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