The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences

Multiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that peptide which links trimerization stalk and catalytic domain can adopt helical, β-strand loop conformations. This region has been called a ‘shape-shifter’ peptide. Characterisation this using NMR experiments MD simulations shown it is essentially disordered in solution. Analysis identifies role intermolecular contacts, within an assembly molecules, stabilising different linker These context-dependent conformational properties may be important functionally, allowing for binding shuffling variety substrates to PmScsC. They also have relevance our understanding aggregation misfolding showing how quaternary interactions lead β-sheet formation by sequence other contexts adopts helical structure. ‘shape-shifting’ reminiscent one-to-many molecular recognition features (MoRFs) found intrinsically proteins are able conformations when they fold upon their partners.