Galectin-4 Antimicrobial Activity Primarily Occurs Through its C-Terminal Domain

作者：Hau-Ming Jan, Shang‐Chuen Wu, Carter J. Stowell, Mary L. Vallecillo-Zúniga, Anu Paul, Kashyap Patel, Sasikala Muthusamy, Hsien‐Ya Lin, Diyoly Ayona, Ryan Philip Jajosky, Samata P. Varadkar, Hirotomo Nakahara, Rita Chan, Devika Bhave, William J. Lane, Melissa Y. Yeung, Marie A. Hollenhorst, Seth Rakoff-Nahoum, Richard D. Cummings, Connie M. Arthur, Sean R. Stowell · 发表于：Molecular & Cellular Proteomics · 年份：2024 · DOI：10.1016/j.mcpro.2024.100747 · 被引用次数：13 · 研究领域：Galectins and Cancer Biology、Toxin Mechanisms and Immunotoxins

Although immune tolerance evolved to reduce reactivity with self, it creates a gap in the adaptive immune response against microbes that decorate themselves in self-like antigens. This is particularly apparent with carbohydrate-based blood group antigens, wherein microbes can envelope themselves in blood group structures similar to human cells. In this study, we demonstrate that the innate immune lectin, galectin-4 (Gal-4), exhibits strain-specific binding and killing behavior towards microbes that display blood group-like antigens. Examination of binding preferences using a combination of microarrays populated with ABO(H) glycans and a variety of microbial strains, including those that express blood group-like antigens, demonstrated that Gal-4 binds mammalian and microbial antigens that have features of blood group and mammalian-like structures. Although Gal-4 was thought to exist as a monomer that achieves functional bivalency through its two linked carbohydrate recognition domains, our data demonstrate that Gal-4 forms dimers and that differences in the intrinsic ability of each domain to dimerize likely influences binding affinity. While each Gal-4 domain exhibited blood group-binding activity, the C-terminal domain (Gal-4C) exhibited dimeric properties, while the N-terminal domain (Gal-4N) failed to similarly display dimeric activity. Gal-4C not only exhibited the ability to dimerize but also possessed higher affinity toward ABO(H) blood group antigens and microbes expre...