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-Structure paper
タイトル | The signalling conformation of the insulin receptor ectodomain. |
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ジャーナル・号・ページ | Nat Commun, Vol. 9, Issue 1, Page 4420, Year 2018 |
掲載日 | 2018年10月24日 |
![]() | Felix Weis / John G Menting / Mai B Margetts / Shu Jin Chan / Yibin Xu / Norbert Tennagels / Paulus Wohlfart / Thomas Langer / Christoph W Müller / Matthias K Dreyer / Michael C Lawrence / ![]() ![]() ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 3.2 - 4.2 Å |
構造データ | |
化合物 | ![]() ChemComp-NAG: |
由来 |
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![]() | SIGNALING PROTEIN / insulin / insulin receptor ectodomain / signal transdution / signal transduction |