Ren, R.; Zhou, X.; He, Y.; Ke, M.; Wu, J.; Liu, X.; Yan, C.; Wu, Y.; Gong, X.; Lei, X.; Yan, S. F.; Radhakrishnan, A.; Yan, N.*
Science 2015, 349, 187-191
Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane–embedded sterol sensors that regulate the?cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited.?Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with […]
Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane–embedded sterol sensors that regulate the?cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited.?Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii. MvINS exists as a homotrimer. Each protomer comprises six transmembrane segments (TMs), with TM3 and TM4 contributing to homotrimerization. The six TMs enclose a V-shaped cavity that can accommodate a diacylglycerol molecule. A homology-based?structural model of human Insig-2, together with biochemical characterizations, suggest that the central cavity of Insig-2??accommodates 25-hydroxycholesterol, whereas TM3 and TM4 engage in Scap binding. These analyses provide an important framework?for further functional and mechanistic understanding of Insig proteins and the sterol regulatory element–binding protein pathway.
Link: http://www.sciencemag.org/content/349/6244/187.full.pdf