Marine Drugs (Aug 2024)

Novel Galectins Purified from the Sponge <i>Chondrilla australiensis</i>: Unique Structural Features and Cytotoxic Effects on Colorectal Cancer Cells Mediated by TF-Antigen Binding

  • Ryuhei Hayashi,
  • Kenichi Kamata,
  • Marco Gerdol,
  • Yuki Fujii,
  • Takashi Hayashi,
  • Yuto Onoda,
  • Nanae Kobayashi,
  • Satoshi Furushima,
  • Ryuya Ishiwata,
  • Mayuka Ohkawa,
  • Naoko Masuda,
  • Yuka Niimi,
  • Masao Yamada,
  • Daisuke Adachi,
  • Sarkar M. A. Kawsar,
  • Sultana Rajia,
  • Imtiaj Hasan,
  • Somrita Padma,
  • Bishnu Pada Chatterjee,
  • Yuji Ise,
  • Riku Chida,
  • Kayo Hasehira,
  • Nobumitsu Miyanishi,
  • Tatsuya Kawasaki,
  • Yukiko Ogawa,
  • Hideaki Fujita,
  • Alberto Pallavicini,
  • Yasuhiro Ozeki

DOI
https://doi.org/10.3390/md22090400
Journal volume & issue
Vol. 22, no. 9
p. 400

Abstract

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We here report the purification of a novel member of the galectin family, the β-galactoside-binding lectin hRTL, from the marine sponge Chondrilla australiensis. The hRTL lectin is a tetrameric proto-type galectin with a subunit molecular weight of 15.5 kDa, consisting of 141 amino acids and sharing 92% primary sequence identity with the galectin CCL from the congeneric species C. caribensis. Transcriptome analysis allowed for the identification of additional sequences belonging to the same family, bringing the total number of hRTLs to six. Unlike most other galectins, hRTLs display a 23 amino acid-long signal peptide that, according to Erdman degradation, is post-translationally cleaved, leaving an N-terminal end devoid of acetylated modifications, unlike most other galectins. Moreover, two hRTLs display an internal insertion, which determines the presence of an unusual loop region that may have important functional implications. The characterization of the glycan-binding properties of hRTL revealed that it had high affinity towards TF-antigen, sialyl TF, and type-1 N-acetyl lactosamine with a Galβ1-3 structure. When administered to DLD-1 cells, a colorectal carcinoma cell line expressing mucin-associated TF-antigen, hRTL could induce glycan-dependent cytotoxicity.

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