The aberrant accumulation of sterols contributes to heart attack and stroke. Two proteins embedded in the membrane of the endoplasmic reticulum, Insig-1 and Insig-2, are key players in the cellular pathway that regulates cellular sterol levels. Ren et al. report the structure of a mycobacterial homolog of Insig. The structure, together with biochemical experiments, suggests how Insig interacts with other components of the sterol regulatory pathway.
R. Ren, X. Zhou, Y. He, M. Ke, J. Wu, X. Liu, C. Yan, Y. Wu, X. Gong, X. Lei, S. F. Yan, A. Radhakrishnan, N. Yan, Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels. Science 349, 187–191 (2015). [Abstract] [Full Text]