title: Cholera toxin B subunits assemble into pentamers--proposition of a fly-casting mechanism.
abstract: The cholera toxin B pentamer (CtxB(5)), which belongs to the AB(5) toxin family, is used as a model study for protein assembly. The effect of the pH on the reassembly of the toxin was investigated using immunochemical, electrophoretic and spectroscopic methods. Three pH-dependent steps were identified during the toxin reassembly: (i) acquisition of a fully assembly-competent fold by the CtxB monomer, (ii) association of CtxB monomer into oligomers, (iii) acquisition of the native fold by the CtxB pentamer. The results show that CtxB(5) and the related heat labile enterotoxin LTB(5) have distinct mechanisms of assembly despite sharing high sequence identity (84%) and almost identical atomic structures. The difference can be pinpointed to four histidines which are spread along the protein sequence and may act together. Thus, most of the toxin B amino acids appear negligible for the assembly, raising the possibility that assembly is driven by a small network of amino acids instead of involving all of them.
authors.affiliation: LAPTH, Université de Savoie, CNRS, Annecy le Vieux, France.
authors.forename: Jihad
authors.initials: J
authors.lastname: Zrimi
authors.forename: Alicia
authors.initials: A
authors.lastname: Ng Ling
authors.forename: Ernawati
authors.initials: E
authors.lastname: Giri-Rachman Arifin
authors.forename: Giovanni
authors.initials: G
authors.lastname: Feverati
authors.forename: Claire
authors.initials: C
authors.lastname: Lesieur
mesh_terms: D000465:Algorithms; D002772:Cholera Toxin / Q000737:chemistry*; D002942:Circular Dichroism; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D004058:Diffusion; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005677:G(M1) Ganglioside / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D055503:Protein Multimerization; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D005677:G(M1) Ganglioside; D006639:Histidine; D002772:Cholera Toxin