8by3

FimH lectin domain in complex with oligomannose-6

spinqualitylabelsall models 8by3, resolution 3.19Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8by3 is a 4 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BMA, MAN, NAG, NI, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FIMH_ECOLI Involved in regulation of length and mediation of adhesion of type 1 fimbriae (but not necessary for the production of fimbriae). Adhesin responsible for the binding to D-mannose. It is laterally positioned at intervals in the structure of the type 1 fimbriae. In order to integrate FimH in the fimbriae FimF and FimG are needed. Publication Abstract from PubMed 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 -5 bind with the highest affinity to FimH by using the same Manalpha1,3Man 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 alpha1,2-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(R) assay. To make the transition to oligomannose-6, we measured the kinetics of FimH binding using paucimannosidic N-glycans, glycoproteins and all four alpha-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 Manalpha1,3Manalpha1 and Manalpha1,6Manalpha1 dimannosides. The binding of core alpha1,6-fucosylated oligomannose-3 in the co-crystals of FimH is monovalent, but interestingly the GlcNAc1 - Fuc moiety retains highly flexibility. In co-crystals with oligomannose-6, two FimH bacterial adhesins bind the Manalpha1,3Manalpha1 and Manalpha1,6Manalpha1 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. Structural insights into a cooperative switch between one and two FimH bacterial adhesins binding pauci- and high-mannose type N-glycan receptors.,Krammer EM, Bridot C, Serna S, Echeverria B, Semwal S, Roubinet B, van Noort K, Wilbers RP, Bourenkov G, de Ruyck J, Landemarre L, Reichardt N, Bouckaert J J Biol Chem. 2023 Mar 19:104627. doi: 10.1016/j.jbc.2023.104627. PMID:36944399 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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