Unraveling the Effect of the C-terminal Tail of Agaricus bisporus Mannose-Binding Protein and Discovery of a Second Functional Sugar-Binding Site

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Anis P. Rahayu^1,a, Zunia R. Akhwan^2,b, Agung H. Karsono^2,c, Hiromi Yoshida^3,d, Ratna A. Utami^1,e, Raymond R. Tjandrawinata^2,4,f, Heni Rachmawati^1,5,g*, and Wangsa T. Ismaya^2,h*

¹School of Pharmacy, Bandung Institute of Technology, Bandung, 40132, Indonesia

²Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, 17550, Indonesia

³Department of Basic Life Science, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan

⁴Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Tangerang, 15345, Indonesia

⁵Center for Nanotechnology and Nanosciences, Bandung Institute of Technology, Bandung, 40132, Indonesia

^* To whom correspondence should be addressed.

Received: July 24, 2025; Revised: October 9, 2025; Accepted: October 9, 2025

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The effect of the C-terminal tail on the bioactivity of Agaricus bisporus mannose-binding protein (Abmb) was investigated. Based on the earlier obtained crystal structure of Abmb, it was suggested that the additional C-terminal tail can modulate the binding of sugars to the protein. According to glycan microarray, Abmb can bind β-Gal sugars, which contradicted the results of SPR analysis showing that Abmb only interacts with α-Man and not with α-Gal. Here, we used MCF-7 and MDA-MB-231 breast cancer cells to demonstrate that the presence of the C-terminal tail decreased the anti-proliferative activity of Abmb. Pre-incubating Abmb with α-Gal did not eliminate the anti-proliferative activity, while pre-incubation with α-Man attenuated it. At the same time, preincubation with a mixture of α-Gal and α-Man strongly promoted the anti-proliferative activity of Abmb. In silico analysis using molecular docking suggested the presence of a second functional sugar-binding site for Gal, which had not been identified previously. The study provides new insights into the structure of lectins and their interaction with sugars

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KEY WORDS: Agaricus bisporus, breast cancer cells, cell proliferation, lectin, mannose-binding protein, sugar-binding site

DOI: 10.1134/S0006297925602229

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