Multimerization-Driven Functional Divergence of Prototype Galectins in the Marine Sponge Chondrilla australiensis
Year: 2026
Type: article
Abstract: Functional divergence among lectins can arise even in the absence of variation in carbohydrate recognition domains (CRDs), yet the underlying mechanisms remain poorly understood. Here, we investigated the structure–function relationships of hRTLs, a family of six prototype galectins from the sponge Chondrilla australiensis. Recombinant hRTLs lacking the predicted 23-amino-acid non-canonical signal peptide were expressed in Escherichia coli and analyzed for glycan-binding specificity using glycan arrays. Four members (hRTL-1, 2, 5, and 6) exhibited glycan-binding activity, whereas hRTL-3 and 4 showed markedly weaker activity. hRTL-1 and 2 displayed similar binding profiles, including recognition of TF-related glycans, while hRTL-5 preferentially bound type-1 LacNAc and hRTL-6 recognized blood group-related glycans. Structural analyses revealed distinct oligomeric states, with dimeric and tetrameric species supported by native mass spectrometry and size-exclusion chromatography, while additional higher-molecular-weight (HMW) species were observed by non-heated SDS–PAGE. Far-UV CD spectroscopy further showed that representative active and low-activity hRTLs retained β-sheet-rich secondary structures. Notably, thermal stability assays showed that multimer-forming hRTLs retained hemagglutination activity after prolonged incubation at 60 °C, whereas non-multimerizing members exhibited reduced stability. These findings show that distinct oligomeric organizations are associated with functional diversification among structurally conserved galectin CRDs and suggest that modulation of multimerization may have contributed to the evolution of early metazoan lectins.
Source: Marine Drugs
DOI: 10.3390/md24110393
Authors: Kenichi Kamata, Yuki Fujii, Marco Gerdol, Daniela Eugenia Nerelli, Atsuji Kodama, Satoshi Odo, Hiyori Hatazawa, Masahiro Kasuya, Namiho Matsuzaki, Keita Yamamoto, Suzuna Yoshimoto, Masao Yamada, Sarkar M. Abe Kawsar, Sultana Rajia, Imtiaj Hasan, Bishnu Pada Chatterjee, Tatsusada Yoshida, Tatsuya Kawasaki, Yukiko Ogawa, Kazuteru Shinozaki, Hideaki Fujita, Susumu Uchiyama, Yasuhiro Ozeki
Institutions: Nihon University, Nagasaki International University, University of Trieste, National Institutes of Natural Sciences, The Exploratory Research Center on Life and Living Systems, Yokohama City University, University of Chittagong, Varendra University, University of Rajshahi, Chittaranjan National Cancer Institute, The University of Osaka
Language: English
Topic: Galectins and Cancer Biology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225167196