Microbial binding module employs sophisticated clustered saccharide patches to selectively adhere to mucins

Jaroentomeechai, Thapakorn ; Veloz, Billy (Universidad de Zaragoza) ; Soares, Cátia O. ; Goerdeler, Felix ; Grosso, Ana Sofia ; Büll, Christian ; Miller, Rebecca L. ; Furukawa, Sanae ; Ginés-Alcober, Irene ; Taleb, Víctor ; Merino, Pedro (Universidad de Zaragoza) ; Ghirardello, Mattia (Universidad de Zaragoza) ; Compañón, Ismael ; Coelho, Helena ; Dias, Jorge S. ; Vincentelli, Renaud ; Henrissat, Bernard ; Joshi, Hiren ; Clausen, Henrik ; Corzana, Francisco ; Marcelo, Filipa ; Hurtado-Guerrero, Ramon ; Narimatsu, Yoshiki

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41467-025-63756-w

Año: 2025

Publicado en: Nature communications 16, 1 (2025), [14 pp.]
ISSN: 2041-1723

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/E34-R17
Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/E34-R23
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP58_18
Financiación: info:eu-repo/grantAgreement/EC/H2020/101034288/EU/International Fellowship Programme for Talent Attraction to the Campus of International Excellence Campus Iberus/IberusExperience
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2021-127622OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-137973NB-I00

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)