4O3Y

Crystal structure of the vaccine antigen Transferrin Binding Protein B (TbpB) mutant Arg-179-Glu from Actinobacillus pleuropneumoniae H87

Summary for 4O3Y

• Entry DOI: 10.2210/pdb4o3y/pdb
• Related: 4O3W 4O3X 4O3Z 4O49 4O4U 4O4X
• Descriptor: Outer membrane protein; transferrin-binding protein, GLYCEROL, ACETATE ION, ... (4 entities in total)
• Functional Keywords: structure-based vaccine design, transferrin receptor, iron acquisition, host pathogen interaction, surface lipoprotein, metal transport
• Biological source: Actinobacillus pleuropneumoniae
• Total number of polymer chains: 1
• Total formula weight: 57830.00

Authors

Calmettes, C.,Yu, R.H.,Schryvers, A.B.,Moraes, T.F. (deposition date: 2013-12-18, release date: 2015-01-14, Last modification date: 2015-03-04)

Primary citation

Frandoloso, R.,Martinez-Martinez, S.,Calmettes, C.,Fegan, J.,Costa, E.,Curran, D.,Yu, R.H.,Gutierrez-Martin, C.B.,Rodriguez-Ferri, E.F.,Moraes, T.F.,Schryvers, A.B.
Nonbinding site-directed mutants of transferrin binding protein B exhibit enhanced immunogenicity and protective capabilities.
Infect.Immun., 83:1030-1038, 2015

PubMed Abstract: Host-adapted Gram-negative bacterial pathogens from the Pasteurellaceae, Neisseriaceae, and Moraxellaceae families normally reside in the upper respiratory or genitourinary tracts of their hosts and rely on utilizing iron from host transferrin (Tf) for growth and survival. The surface receptor proteins that mediate this critical iron acquisition pathway have been proposed as ideal vaccine targets due to the critical role that they play in survival and disease pathogenesis in vivo. In particular, the surface lipoprotein component of the receptor, Tf binding protein B (TbpB), had received considerable attention as a potential antigen for vaccines in humans and food production animals but this has not translated into the series of successful vaccine products originally envisioned. Preliminary immunization experiments suggesting that host Tf could interfere with development of the immune response prompted us to directly address this question with site-directed mutant proteins defective in binding Tf. Site-directed mutants with dramatically reduced binding of porcine transferrin and nearly identical structure to the native proteins were prepared. A mutant Haemophilus parasuis TbpB was shown to induce an enhanced B-cell and T-cell response in pigs relative to native TbpB and provide superior protection from infection than the native TbpB or a commercial vaccine product. The results indicate that binding of host transferrin modulates the development of the immune response against TbpBs and that strategies designed to reduce or eliminate binding can be used to generate superior antigens for vaccines.

PubMed: 25547790
DOI: 10.1128/IAI.02572-14

Experimental method

X-RAY DIFFRACTION (2.6 Å)