6HN4

Leucine-zippered human insulin receptor ectodomain with single bound insulin - "lower" membrane-proximal part

6HN4 の概要

• エントリーDOI: 10.2210/pdb6hn4/pdb
• EMDBエントリー: 0246
• 分子名称: Insulin receptor,Insulin receptor,General control protein GCN4, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: insulin, insulin receptor ectodomain, signal transdution, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 214783.67

構造登録者

Weis, F.,Menting, J.G.,Margetts, M.B.,Chan, S.J.,Xu, Y.,Tennagels, N.,Wohlfart, P.,Langer, T.,Mueller, C.W.,Dreyer, M.K.,Lawrence, M.C. (登録日: 2018-09-14, 公開日: 2018-11-21, 最終更新日: 2024-11-13)

主引用文献

Weis, F.,Menting, J.G.,Margetts, M.B.,Chan, S.J.,Xu, Y.,Tennagels, N.,Wohlfart, P.,Langer, T.,Muller, C.W.,Dreyer, M.K.,Lawrence, M.C.
The signalling conformation of the insulin receptor ectodomain.
Nat Commun, 9:4420-4420, 2018

PubMed Abstract: Understanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy structure of a single insulin bound to a physiologically relevant, high-affinity version of the receptor ectodomain, the latter generated through attachment of C-terminal leucine zipper elements to overcome the conformational flexibility associated with ectodomain truncation. The resolution of the cryo-electron microscopy maps is 3.2 Å in the insulin-binding region and 4.2 Å in the membrane-proximal region. The structure reveals how the membrane proximal domains of the receptor come together to effect signalling and how insulin's negative cooperativity of binding likely arises. Our structure further provides insight into the high affinity of certain super-mitogenic insulins. Together, these findings provide a new platform for insulin analog investigation and design.

PubMed: 30356040
DOI: 10.1038/s41467-018-06826-6

実験手法

ELECTRON MICROSCOPY (4.2 Å)