Cholera toxin B subunits assemble into pentamers - proposition of a fly-casting mechanism

Zrimi , Jihad
        . LAPTH Laboratoire d'Annecy-le-Vieux de Physique Théorique - 9 Chemin de Bellevue - BP 110 74941 ANNECY LE VIEUX CEDEX FRLCBM Laboratoire de Chimie Bioorganique et Macromoléculaire -  MA; Ng Ling , Alicia
         . Physics Department -  SG; Giri-Rachman Arifin , Ernawati
        . School of life sciences and technology, Bandung; Feverati , Giovanni
        . LAPTH Laboratoire d'Annecy-le-Vieux de Physique Théorique - 9 Chemin de Bellevue - BP 110 74941 ANNECY LE VIEUX CEDEX FR; Lesieur , Claire
         Institut National de la Recherche Agronomique, ANNECY LE VIEUXGRENOBLE . LAPTH Laboratoire d'Annecy-le-Vieux de Physique Théorique - 9 Chemin de Bellevue - BP 110 74941 ANNECY LE VIEUX CEDEX FRPhysics Department -  SGiRTSV institut de Recherches en Technologies et Sciences pour le Vivant - bat. C3 17 Rue des martyrs 38054 GRENOBLE CEDEX 9 FR

Cholera toxin B subunits assemble into pentamers - proposition of a fly-casting mechanism

2010

Zrimi , Jihad (Centre National de la Recherche ScientifiqueUniversity Cadi Ayyad - UCA, ANNECY LE VIEUX(France). LAPTH Laboratoire d'Annecy-le-Vieux de Physique Théorique - 9 Chemin de Bellevue - BP 110 74941 ANNECY LE VIEUX CEDEX FRLCBM Laboratoire de Chimie Bioorganique et Macromoléculaire - MA) | Ng Ling , Alicia (National University of Singapore (NUS) (Singapour). Physics Department - SG) | Giri-Rachman Arifin , Ernawati (Institut Teknologi Bandung , Bandung (Indonésie). School of life sciences and technology, Bandung ) | Feverati , Giovanni (Centre National de la Recherche Scientifique, ANNECY LE VIEUX(France). LAPTH Laboratoire d'Annecy-le-Vieux de Physique Théorique - 9 Chemin de Bellevue - BP 110 74941 ANNECY LE VIEUX CEDEX FR) | Lesieur , Claire (Centre National de la Recherche ScientifiqueNational University of Singapore (NUS) Institut National de la Recherche Agronomique, ANNECY LE VIEUXGRENOBLE (France). LAPTH Laboratoire d'Annecy-le-Vieux de Physique Théorique - 9 Chemin de Bellevue - BP 110 74941 ANNECY LE VIEUX CEDEX FRPhysics Department - SGiRTSV institut de Recherches en Technologies et Sciences pour le Vivant - bat. C3 17 Rue des martyrs 38054 GRENOBLE CEDEX 9 FR)

The cholera toxin B pentamer (CtxB5), which belongs to the AB5 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 CtxB5 and the related heat labile enterotoxin LTB5 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.

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