@article{3165,
  keywords = {Bacterial Proteins, Humans, Membrane Proteins, Crystallography, X-Ray, Protein Structure, Secondary, Protein Multimerization, Diglycerides, Hydroxycholesterols, Intracellular Signaling Peptides and Proteins, Mycobacterium, Sterol Regulatory Element Binding Proteins},
  author = {Ruobing Ren and Xinhui Zhou and Yuan He and Meng Ke and Jianping Wu and Xiaohui Liu and Chuangye Yan and Yixuan Wu and Xin Gong and Xiaoguang Lei and S Frank Yan and Arun Radhakrishnan and Nieng Yan},
  title = {PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels.},
  abstract = { <p>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.</p> },
  year = {2015},
  journal = {Science},
  volume = {349},
  pages = {187-91},
  month = {2015 Jul 10},
  issn = {1095-9203},
  doi = {10.1126/science.aab1091},
  language = {eng},
}