New Insights into the Molecular Mechanism of Beta Barrel Outer Membrane Protein Folding

Abstract

Inspired by the seminal work of Anfinsen, investigations of the folding of small, water-soluble proteins have culminated in detailed insights into how these molecules attain and stabilise their native folds. In contrast, despite their overwhelming importance in biology, progress in understanding the folding and stability of membrane proteins remains relatively limited. Focusing on the β-barrel outer membrane protein, PagP, we have been using mutational analysis to determine how this protein folds from its urea denatured state into lipid vesicles and how this process is facilitated by molecular chaperones. In this lecture I will describe our recent experiments that have investigated the initial interactions of PagP with a bilayer, its mechanism of insertion into lipid, and how this process is facilitated by the molecular chaperones skp and surA. The work is at an early stage compared with the plethora of knowledge about the folding of water soluble proteins and how this is assisted by chaperones. Nonetheless the folding of this membrane protein is revealing new insights, new challenges and fascinating synergies with the folding mechanisms of water soluble counterparts.ReferencesHuysmans, G., Radford, S.E., Brockwell, D.J. & Baldwin, S.A. (2007) J. Mol. Biol. 373, 529-540Huysmans, G., Baldwin, S.A., Brockwell, D.J. & Radford, S.E. (2010) PNAS 107, 4099-4104Huysmans, G., Radford, S.E., Baldwin, S.A., Brockwell, D.J. (2012) J. Mol. Biol. 416, 453-464