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Molecular Insights into O-Linked Sialoglycans Recognition by the Siglec-Like SLBR-N (SLBRUB10712) of Streptococcus gordonii

文献类型:期刊论文

作者Di Carluccio, Cristina14; Cerofolini, Linda12,13; Moreira, Miguel14; Rosu, Frederic10,11; Padilla-Cortes, Luis12,13; Gheorghita, Giulia Roxana9,12,13; Xu, Zhuojia8; Santra, Abhishek6,7; Yu, Hai7; Yokoyama, Shinji5
刊名ACS CENTRAL SCIENCE
出版日期2024-02-07
卷号10期号:2页码:447-459
ISSN号2374-7943
DOI10.1021/acscentsci.3c01598
通讯作者Marchetti, Roberta(roberta.marchetti@unina.it) ; Silipo, Alba(silipo@unina.it)
英文摘要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 alpha 2,3-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.
WOS关键词SURFACE GLYCOPROTEINS GSPB ; BINDING ; HSA
资助项目National Natural Science Foundation of China[956758] ; CERM/CIRMMP Italy centre[PRIN2017] ; CERM/CIRMMP Italy centre[2017XZ2ZBK] ; CERM/CIRMMP Italy centre[2019-2023] ; CERM/CIRMMP Italy centre[2022ZEZS45] ; Ministry of Education, Universities and Research[R01AI130684] ; United States National Institutes of Health (NIH)[R03 DE029516] ; NIH[22077130] ; National Natural Science Foundation of China[851356] ; European Research Council (ERC) under the European Union[PE00000007] ; Missione 4 - Componente 2 - NextGenerationEU - Partenariato Esteso INF-ACT - One Health Basic and Translational Research Actions Addressing Unmet Needs on Emerging Infectious Diseases MUR
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001177897000001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/310387]  
专题中国科学院上海药物研究所
通讯作者Marchetti, Roberta; Silipo, Alba
作者单位1.Univ Calif San Francisco, San Francisco, CA 94121 USA
2.San Francisco VA Med Ctr, San Francisco, CA 94121 USA
3.Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2R3, Canada
4.Univ Alberta, Dept Chem, Edmonton, AB T6G 2R3, Canada
5.Osaka Univ, Grad Sch Sci, Osaka 5650871, Japan
6.CSIR Indian Inst Chem Technol, Dept Organ Synth & Proc Chem, Uppal Rd, Hyderabad 500007, India
7.Univ Calif Davis, Dept Chem, Davis, CA 95616 USA
8.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
9.Giotto Biotech Srl, I-50019 Sesto Fiorentino, Italy
10.Univ Geneva, Spectrometrie Masse Bioanalyt Sect Sci Pharmaceut, CH-1211 Geneva 4, Switzerland
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GB/T 7714
Di Carluccio, Cristina,Cerofolini, Linda,Moreira, Miguel,et al. Molecular Insights into O-Linked Sialoglycans Recognition by the Siglec-Like SLBR-N (SLBRUB10712) of Streptococcus gordonii[J]. ACS CENTRAL SCIENCE,2024,10(2):447-459.
APA Di Carluccio, Cristina.,Cerofolini, Linda.,Moreira, Miguel.,Rosu, Frederic.,Padilla-Cortes, Luis.,...&Silipo, Alba.(2024).Molecular Insights into O-Linked Sialoglycans Recognition by the Siglec-Like SLBR-N (SLBRUB10712) of Streptococcus gordonii.ACS CENTRAL SCIENCE,10(2),447-459.
MLA Di Carluccio, Cristina,et al."Molecular Insights into O-Linked Sialoglycans Recognition by the Siglec-Like SLBR-N (SLBRUB10712) of Streptococcus gordonii".ACS CENTRAL SCIENCE 10.2(2024):447-459.

入库方式: OAI收割

来源:上海药物研究所

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