Chemistry Researchers Discover Novel Strategies to Control Protein Folding Pathways

Former Chemistry graduate student Alireza Ghanbarpour and co-workers, under the direction of Professors Babak Borhan and James H. Geiger have had their article, Human Cellular Retinol Binding Protein II Forms a Domain‐Swapped Trimer Representing a Novel Fold and a New Template for Protein Engineering, highlighted on the Cover of the October 2020 issue of ChemBioChem. 

The article describes how the folding pathway of human cellular retinol binding protein II was manipulated to favor formation of a domain-swapped trimer, a previously unknown structure, by rational protein engineering of a cross-subunit disulfide bond. The three-fold symmetry of the trimer was then exploited in the design of a high-affinity zinc binding site by introduction of a single mutation, thus demonstrating the potential of the trimer as a new protein design template.