Sigma Proteins: Evolution of the Concept of Sigma Receptors

Andrew Kruse, Kruse, Andrew

Sigma1 (also known as this sigma-1 receptor) is an unusual and enigmatic transmembrane protein implicated in a diverse array of biological processes ranging from neurodegenerative disease to cancer. Despite decades of research, the molecular architecture of Sigma1 is only beginning to become clear. Recent work has established that Sigma1 is an oligomer, and crystallographic studies have now offered the first high-resolution views of its molecular structure. For the first time, these results provide a detailed framework to understand mutagenesis data and the molecular pharmacology of Sigma1 ligands. Structural data also raise new questions surrounding the mechanisms of ligand activity and the molecular basis for interactions between Sigma1 and other proteins. As Sigma1 research enters the structural era, the field is poised for new discoveries and reevaluation of old data and old models.