New Insights on Protein Folding and Misfolding: Histidine Behaviors.

Abstract

Protein folding is crucial as it determines the three-dimensional structure and function of proteins, which are essential for biological processes, while misfolding can lead to the formation of aggregates and dysfunctional proteins, often associated with diseases. Histidine behaviors have been identified as a contributing factor to protein folding and misfolding due to changes in net charge and the diverse orientations of N/N-H groups on imidazole rings. In this viewpoint, we discuss misfolding diseases, the fundamental principles of histidine behaviors, and relevant studies in this field. Our current study helps elucidate histidine behaviors and their impact on secondary structure and aggregation characteristics, offering new insights into the mechanisms of histidine-related protein folding and misfolding.