Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain

作者：Croll Tristan I; Smith Brian J; Margetts Mai B; Whittaker Jonathan; Weiss Michael A; Ward Colin W; Lawrence Michael C^*

来源：Structure, 2016, 24(3): 469-476.

DOI：10.1016/j.str.2015.12.014

Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 angstrom) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 angstrom resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.

• 出版日期2016-3-1
• 单位河北医科大学