Microbial binding module employs sophisticated clustered saccharide patches to selectively adhere to mucins
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.
Authors
- Felix Goerdeler (ORCID: https://orcid.org/0000-0002-7190-9145)
- Hiren J. Joshi (ORCID: https://orcid.org/0000-0002-8192-2829)
- Christian Büll (ORCID: https://orcid.org/0000-0001-7785-2920)
- Yoshiki Narimatsu (ORCID: https://orcid.org/0000-0003-1428-5695)
- Jorge S. Dias (ORCID: https://orcid.org/0000-0001-9725-1882)
- Cátia O. Soares
- Thapakorn Jaroentomeechai (ORCID: https://orcid.org/0000-0003-2235-7820)
- Víctor Taleb (ORCID: https://orcid.org/0000-0001-9224-5854)
- Pedro Merino (ORCID: https://orcid.org/0000-0002-2202-3460)
- Mattia Ghirardello (ORCID: https://orcid.org/0000-0002-2855-4801)
- Renaud Vincentelli (ORCID: https://orcid.org/0000-0001-9667-0196)
- Henrik Clausen (ORCID: https://orcid.org/0000-0002-0915-5055)
- Bernard Henrissat (ORCID: https://orcid.org/0000-0002-3434-8588)
- Filipa Marcelo (ORCID: https://orcid.org/0000-0001-5049-8511)
- Ana Sofia Grosso (ORCID: https://orcid.org/0000-0001-5324-4998)
- Ismael Compañón (ORCID: https://orcid.org/0000-0002-2440-2958)
- Ramón Hurtado‐Guerrero (ORCID: https://orcid.org/0000-0002-3122-9401)
- Helena Coelho (ORCID: https://orcid.org/0000-0003-1992-8557)
- Francisco Corzana (ORCID: https://orcid.org/0000-0001-5597-8127)
- Rebecca L. Miller (ORCID: https://orcid.org/0000-0001-8574-1948)
- Billy Veloz
- Sanae Furukawa
- Irene Ginés‐Alcober
Institutions
- University of Copenhagen (DK)
- Radboud University Nijmegen (NL)
- Universidad de La Rioja (ES)
- Aix-Marseille Université (FR)
- Universidad de Zaragoza (ES)
- Radboud University Medical Center (NL)
- Fundacion Agencia Aragonesa para la Investigacion y el Desarrollo (ES)
- Radboud Institute for Molecular Life Sciences (NL)
- YKK (Japan) (JP)
- Architecture et Fonction des Macromolécules Biologiques (FR)
- Biocom (US)
- Unidade em Ciências Biomoleculares Aplicadas
- Universidade Nova de Lisboa (PT)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1038/s41467-025-63756-w
- Citations
- 2
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Ministerio de Ciencia, Innovación y Universidades
- National Research Foundation
- Danmarks Grundforskningsfond
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Lundbeckfonden
- Novo Nordisk
- Universidad de Zaragoza
- Novo Nordisk Fonden
- Gobierno de Aragón
- H. Lundbeck A/S
- Applied Molecular Biosciences Unit
- Universidad de La Rioja
- National Institutes of Health
- Fundação para a Ciência e a Tecnologia
- National Institute of General Medical Sciences