9f21

Crystal structure of Borrelia burgdorferi CspZ-YACS

spinqualitylabelsall models 9f21, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9f21 is a 1 chain structure with sequence from Borreliella burgdorferi B31. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function O50665_BORBU Publication Abstract from PubMed Borrelia burgdorferi (Bb) causes Lyme disease (LD), one of the most common vector-borne diseases in the Northern Hemisphere. Here, we solve the crystal structure of a mutated Bb vaccine antigen, CspZ-YA that lacks the ability to bind to host complement factor H (FH). We generate point mutants of CspZ-YA and identify CspZ-YA(I183Y) and CspZ-YA(C187S) to trigger more robust bactericidal responses. Compared to CspZ-YA, these CspZ-YA mutants require a lower immunization frequency to protect mice from LD-associated inflammation and bacterial colonization. Antigenicity of wild-type and mutant CspZ-YA proteins are similar, as measured using sera from infected people or immunized female mice. Structural comparison of CspZ-YA with CspZ-YA(I183Y) and CspZ-YA(C187S) shows enhanced interactions of two helices adjacent to the FH-binding sites in the mutants, consistent with their elevated thermostability. In line with these findings, protective CspZ-YA monoclonal antibodies show increased binding to CspZ-YA at a physiological temperature (37 degrees C). In summary, this proof-of-concept study applies structural vaccinology to enhance intramolecular interactions for the long-term stability of a Bb antigen while maintaining its protective epitopes, thus promoting LD vaccine development. Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine.,Brangulis K, Malfetano J, Marcinkiewicz AL, Wang A, Chen YL, Lee J, Liu Z, Yang X, Strych U, Tupina D, Akopjana I, Bottazzi ME, Pal U, Hsieh CL, Chen WH, Lin YP Nat Commun. 2025 Apr 7;16(1):2898. doi: 10.1038/s41467-025-58182-x. PMID:40189575 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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