9F1V

Crystal structure of Borrelia burgdorferi CspZ-YA

Summary for 9F1V

• Entry DOI: 10.2210/pdb9f1v/pdb
• Descriptor: Complement regulator-acquiring surface protein 2 (CRASP-2) (2 entities in total)
• Functional Keywords: complement-binding protein; lyme disease; borreliosis, immune system
• Biological source: Borreliella burgdorferi B31
• Total number of polymer chains: 1
• Total formula weight: 25169.71

Authors

Brangulis, K.,Malfetano, J.,Marcinkiewicz, A.L.,Wang, A.,Chen, Y.-L.,Yang, X.,Lee, W.,Bottazzi, M.-E.,Pal, U.,Hsieh, C.-L.,Chen, W.-H.,Lin, Y.-P. (deposition date: 2024-04-20, release date: 2025-04-16)

Primary citation

Brangulis, K.,Malfetano, J.,Marcinkiewicz, A.L.,Wang, A.,Chen, Y.L.,Lee, J.,Liu, Z.,Yang, X.,Strych, U.,Tupina, D.,Akopjana, I.,Bottazzi, M.E.,Pal, U.,Hsieh, C.L.,Chen, W.H.,Lin, Y.P.
Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine.
Nat Commun, 16:2898-2898, 2025

PubMed Abstract: 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 and CspZ-YA 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 and CspZ-YA 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 °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.

PubMed: 40189575
DOI: 10.1038/s41467-025-58182-x

Experimental method

X-RAY DIFFRACTION (1.9 Å)