4z3t

Meningococcal Factor H binding protein mutant L130R/G133D

spinqualitylabelsall models 4z3t, resolution 1.62Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4z3t is a 2 chain structure with sequence from Neisseria meningitidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.62Å Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6VS32_NEIME Publication Abstract from PubMed Factor H binding protein (FHbp) is part of two vaccines recently licensed for prevention of sepsis and meningitis caused by serogroup B meningococci. FHbp is classified in three phylogenic variant groups that have limited antigenic cross-reactivity, and FHbp variants in one of the groups have low thermal stability. In the present study, we replaced two amino acid residues, R130 and D133, in a stable FHbp variant with their counterparts (L and G) from a less stable variant. The single and double mutants decreased thermal stability of the amino- (N-) terminal domain compared with the wild-type protein as measured by scanning calorimetry. We introduced the converse substitutions, L130R and G133D, in a less stable wild-type FHbp variant, which increased the transition midpoint (Tm) for the N-terminal domain by 8 and 12 degrees C; together the substitutions increased the Tm by 21 degrees C. We determined the crystal structure of the double mutant FHbp to 1.6 A resolution, which showed that R130 and D133 mediated multiple electrostatic interactions. Monoclonal antibodies specific for FHbp epitopes in the N-terminal domain had higher binding affinity for the recombinant double mutant by surface plasmon resonance and to the mutant expressed on meningococci by flow cytometry. The double mutant also had decreased binding of human complement Factor H, which in previous studies increased the protective antibody responses. The stabilized mutant FHbp thus has the potential to stabilize protective epitopes and increase the protective antibody responses to recombinant FHbp vaccines or native outer membrane vesicle vaccines with overexpressed FHbp. A meningococcal vaccine antigen engineered to increase thermal stability and stabilize protective epitopes.,Konar M, Pajon R, Beernink PT Proc Natl Acad Sci U S A. 2015 Dec 1;112(48):14823-8. doi:, 10.1073/pnas.1507829112. Epub 2015 Nov 16. PMID:26627237 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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