Mini-review Cholera and Shiga toxin B-subunits: thermodynamic and structural considerations for function and biomedical applications David G. Pina, Ludger Johannes * Laboratoire Trafic et Signalisation, UMR 144 Curie/CNRS, Institut Curie, 26 rue d’Ulm, 75248 Paris Cedex 05, France Available online 29 January 2005 Abstract The B-subunits of cholera and Shiga toxins are functionally and structurally related proteins with different chain lengths and no sequence similarity. They are responsible for toxin binding to specific glycosphingolipid receptors and intracellular toxin trafficking. Indeed, it is clearly established that B-subunits have the unique capacity of targeting the toxins to a poorly explored intracellular pathway, the retrograde route, allowing the transfer to the cytosol of the associated catalytic A-subunits, by retro-translocation from the endoplasmic reticulum. The B-subunits have also been used as vectors for antigen presentation in immunotherapeutic approaches. It is, however, not known if and how the B-subunits intervene in membrane translocation of the A-subunits and/or antigens to the cytosol. Therefore, it is important to characterise the driving force of pentamer formation, its conformational stability, and toxin–receptor interactions. This review summarises recent studies that have dealt with these topics. q 2005 Elsevier Ltd. All rights reserved. Keywords: Cholera toxin; Shiga toxin; Receptor binding; Structural stability Contents 1. Introduction: structure and function of cholera and Shiga toxins ...................................... 390 2. Structural stability of CTxB and G M1 receptor binding ............................................. 390 3. Structural stability of STxB and Gb 3 receptor binding ............................................. 391 4. Perspectives ............................................................................ 391 Acknowledgements ...................................................................... 392 References ............................................................................. 392 0041-0101/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.toxicon.2004.12.014 Toxicon 45 (2005) 389–393 www.elsevier.com/locate/toxicon * Corresponding author. Tel.: C33 1 4234 6351; fax: C33 1 4234 6507. E-mail address: johannes@curie.fr (L. Johannes).