Microbial binding module employs sophisticated clustered saccharide patches to selectively adhere to mucins
Thapakorn Jaroentomeechai, Billy Veloz, Cátia O. Soares, Felix Goerdeler, Ana Sofia Grosso, Christian Büll, Rebecca L. Miller, Sanae Furukawa, Irene Ginés-Alcober, Víctor Taleb, Pedro Merino, Mattia Ghirardello, Ismael Compañón, Helena Coelho, Jorge S. Dias, Renaud Vincentelli, Bernard Henrissat, Hiren Joshi, Henrik Clausen, Francisco Corzana, Filipa Marcelo, Ramon Hurtado-Guerrero* & Yoshiki Narimatsu*. Nature Communications volume 16, Article number: 9058 (2025). * joint corresponding authorship
The mucus lining wet body surfaces forms the interphase and barrier for the microbiota and resident microbiomes. Large mucin proteins densely decorated with O-glycans make up the mucus lining to entrap, feed and shape the microbiota, and repress biofilm formation and virulence. How mucins exert these effects is poorly understood and critical is how the microbiota recognize, sense, and break down mucins. Here, we provide structural molecular evidence that a small mucin-binding module designated X409 recognizes clustered saccharide patches comprised of rows of inner monosaccharides in adjacent O-glycans. These patches are unique to mucins and binding to these provides an elegant mechanism to retain adherence to mucins despite trimming of O-glycans during microbial scavenging of monosaccharides from mucins. Realization of clustered saccharide patch-binding motifs provides a hitherto overlooked scenario of contextual glycan epitopes and impetus for discovery of new classes of glycan-binding proteins.
The mucus lining wet body surfaces forms the interphase and barrier for the microbiota and resident microbiomes. Large mucin proteins densely decorated with O-glycans make up the mucus lining to entrap, feed and shape the microbiota, and repress biofilm formation and virulence. How mucins exert these effects is poorly understood and critical is how the microbiota recognize, sense, and break down mucins. Here, we provide structural molecular evidence that a small mucin-binding module designated X409 recognizes clustered saccharide patches comprised of rows of inner monosaccharides in adjacent O-glycans. These patches are unique to mucins and binding to these provides an elegant mechanism to retain adherence to mucins despite trimming of O-glycans during microbial scavenging of monosaccharides from mucins. Realization of clustered saccharide patch-binding motifs provides a hitherto overlooked scenario of contextual glycan epitopes and impetus for discovery of new classes of glycan-binding proteins.