6ro0 | pdb_00006ro0
CRYSTAL STRUCTURE OF GENETICALLY DETOXIFIED PERTUSSIS TOXIN GDPT.
Structural highlights
FunctionTOX3_BORPE PTX oligomer B binds to receptors on the eukaryotic cell surface and facilitates the translocation of the toxic subunit across the cell membrane. Publication Abstract from PubMedThe mutant gdPT R9K/E129G is a genetically detoxified variant of the pertussis toxin (PTx) and represents an attractive candidate for the development of improved pertussis vaccines. The impact of the mutations on the overall protein structure and its immunogenicity has remained elusive. Here we present the crystal structure of gdPT and show that it is nearly identical to that of PTx. Hydrogen-deuterium exchange mass spectrometry revealed dynamic changes in the catalytic domain that directly impacted NAD(+) binding which was confirmed by biolayer interferometry. Distal changes in dynamics were also detected in S2-S5 subunit interactions resulting in tighter packing of B-oligomer corresponding to increased thermal stability. Finally, antigen stimulation of human whole blood, analyzed by a previously unreported mass cytometry assay, indicated broader immunogenicity of gdPT compared to pertussis toxoid. These findings establish a direct link between the conserved structure of gdPT and its ability to generate a robust immune response. Genetically detoxified pertussis toxin displays near identical structure to its wild-type and exhibits robust immunogenicity.,Ausar SF, Zhu S, Duprez J, Cohen M, Bertrand T, Steier V, Wilson DJ, Li S, Sheung A, Brookes RH, Pedyczak A, Rak A, Andrew James D Commun Biol. 2020 Aug 5;3(1):427. doi: 10.1038/s42003-020-01153-3. PMID:32759959[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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