Cristina Di Carluccio, Linda Cerofolini, Miguel Moreira, Frédéric Rosu, Luis Padilla-Cortés, Giulia Roxana Gheorghita, Zhuojia Xu, Abhishek Santra, Hai Yu, Shinji Yokoyama, Taylor E. Gray, Chris D. St. Laurent, Yoshiyuki Manabe, Xi Chen, Koichi Fukase, Matthew S. Macauley, Antonio Molinaro, Tiehai Li, Barbara A. Bensing, Roberta Marchetti*, Valérie Gabelica, Marco Fragai and Alba Silipo*,
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引用次数: 0
Abstract
Streptococcus gordonii is a Gram-positive bacterial species that typically colonizes the human oral cavity, but can also cause local or systemic diseases. Serine-rich repeat (SRR) glycoproteins exposed on the S. gordonii bacterial surface bind to sialylated glycans on human salivary, plasma, and platelet glycoproteins, which may contribute to oral colonization as well as endocardial infections. Despite a conserved overall domain organization of SRR adhesins, the Siglec-like binding regions (SLBRs) are highly variable, affecting the recognition of a wide range of sialoglycans. SLBR-N from the SRR glycoprotein of S. gordonii UB10712 possesses the remarkable ability to recognize complex core 2 O-glycans. We here employed a multidisciplinary approach, including flow cytometry, native mass spectrometry, isothermal titration calorimetry, NMR spectroscopy from both protein and ligand perspectives, and computational methods, to investigate the ligand specificity and binding preferences of SLBR-N when interacting with mono- and disialylated core 2 O-glycans. We determined the means by which SLBR-N preferentially binds branched α2,3-disialylated core 2 O-glycans: a selected conformation of the 3′SLn branch is accommodated into the main binding site, driving the sTa branch to further interact with the protein. At the same time, SLBR-N assumes an open conformation of the CD loop of the glycan-binding pocket, allowing one to accommodate the entire complex core 2 O-glycan. These findings establish the basis for the generation of novel tools for the detection of specific complex O-glycan structures and pave the way for the design and development of potential therapeutics against streptococcal infections.
A multidisciplinary approach combining NMR spectroscopy, native mass spectrometry, flow cytometry, ITC and MD simulation unveiled the binding details of core 2 O-glycans to the Siglec-like adhesin SLBR-N of S. gordonii.
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.