title: An asymmetric and slightly dimerized structure for the tetanus toxoid protein used in glycoconjugate vaccines.
abstract: Tetanus toxoid protein has been characterized with regard oligomeric state and hydrodynamic (low-resolution) shape, important parameters with regard its use in glycoconjugate vaccines. From sedimentation velocity and sedimentation equilibrium analysis in the analytical ultracentrifuge tetanus toxoid protein is shown to be mostly monomeric in solution (~86%) with approximately 14% dimer. The relative proportions do not appear to change significantly with concentration, suggesting the two components are not in reversible equilibrium. Hydrodynamic solution conformation studies based on high precision viscometry, combined with sedimentation data show the protein to be slightly extended conformation in solution with an aspect ratio ~3. The asymmetric structure presents a greater surface area for conjugation with polysaccharide than a more globular structure, underpinning its popular choice as a conjugation protein for glycoconjugate vaccines.
authors.affiliation: National Centre for Macromolecular Hydrodynamics, University of Nottingham, Sutton Bonington LE12 5RD, UK.
authors.forename: Ali Saber
authors.initials: AS
authors.lastname: Abdelhameed
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Morris
authors.forename: Gary G
authors.initials: GG
authors.lastname: Adams
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Rowe
authors.forename: Olivier
authors.initials: O
authors.lastname: Laloux
authors.forename: Louis
authors.initials: L
authors.lastname: Cerny
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonnier
authors.forename: Pierre
authors.initials: P
authors.lastname: Duvivier
authors.forename: Karel
authors.initials: K
authors.lastname: Conrath
authors.forename: Christophe
authors.initials: C
authors.lastname: Lenfant
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Harding
mesh_terms: D002850:Chromatography, Gel; D006001:Glycoconjugates; D008970:Molecular Weight; D055503:Protein Multimerization; D053838:Scattering, Small Angle; D013745:Tetanus Toxoid / Q000737:chemistry*; D014461:Ultracentrifugation; D018074:Vaccines, Conjugate / Q000737:chemistry*; D014783:Viscosity
chemical_list: D006001:Glycoconjugates; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate