دورية أكاديمية
Structural insights into a cooperative switch between one and two FimH bacterial adhesins binding pauci- and high-mannose type N-glycan receptors
| العنوان: | Structural insights into a cooperative switch between one and two FimH bacterial adhesins binding pauci- and high-mannose type N-glycan receptors |
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| المؤلفون: | Krammer, Eva-Maria, Bridot, Clarisse, Serna, Sonia, Echeverria, Begoña, Semwal, Shubham, Roubinet, Benoît, van Noort, Kim, Wilbers, Ruud H.P., Bourenkov, Gleb, de Ruyck, Jérôme, Landemarre, Ludovic, Reichardt, Niels, Bouckaert, Julie |
| المصدر: | Journal of Biological Chemistry 299 (2023) 5 ; ISSN: 0021-9258 |
| سنة النشر: | 2023 |
| المجموعة: | Wageningen UR (University & Research Centre): Digital Library |
| مصطلحات موضوعية: | FimH, N-glycan, bacterial adhesion, cooperativity, core fucose, crystal structure, kinetics, multivalency, oligomannose-3, oligomannose-6, paucimannose |
| الوصف: | The FimH type-1 fimbrial adhesin allows pathogenic Escherichia coli to adhere to glycoproteins in the epithelial linings of human bladder and intestinal tract, by using multiple fimbriae simultaneously. Pauci- and high-mannose type N-glycans are natural FimH receptors on those glycoproteins. Oligomannose-3 and oligomannose-5 bind with the highest affinity to FimH by using the same Manα1,3Man branch. Oligomannose-6 is generated from oligomannose-5 in the next step of the biogenesis of high-mannose N-glycans, by the transfer of a mannose in α1,2-linkage onto this branch. Using serial crystallography and by measuring the kinetics of binding, we demonstrate that shielding the high-affinity epitope drives the binding of multiple FimH molecules. First, we profiled FimH glycan binding on a microarray containing paucimannosidic N-glycans and in a FimH LEctPROFILE assay. To make the transition to oligomannose-6, we measured the kinetics of FimH binding using paucimannosidic N-glycans, glycoproteins and all four α-dimannosides conjugated to bovine serum albumin. Equimolar mixed interfaces of the dimannosides present in oligomannose-6 and molecular dynamics simulations suggest a positive cooperativity in the bivalent binding of Manα1,3Manα1 and Manα1,6Manα1 dimannosides. The binding of core α1,6-fucosylated oligomannose-3 in cocrystals of FimH is monovalent but interestingly the GlcNAc1—Fuc moiety retains highly flexibility. In cocrystals with oligomannose-6, two FimH bacterial adhesins bind the Manα1,3Manα1 and Manα1,6Manα1 endings of the second trimannose core (A-4′-B). This cooperative switch towards bivalent binding appears sustainable beyond a molar excess of oligomannose-6. Our findings provide important novel structural insights for the design of multivalent FimH antagonists that bind with positive cooperativity. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://edepot.wur.nl/629767Test; https://research.wur.nl/en/publications/structural-insights-into-a-cooperative-switch-between-one-and-twoTest |
| DOI: | 10.1016/j.jbc.2023.104627 |
| الإتاحة: | https://doi.org/10.1016/j.jbc.2023.104627Test https://research.wur.nl/en/publications/structural-insights-into-a-cooperative-switch-between-one-and-twoTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ ; Wageningen University & Research |
| رقم الانضمام: | edsbas.3C78B7C4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jbc.2023.104627 |
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