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-Structure paper
タイトル | Structural basis of Notch recognition by human γ-secretase. |
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ジャーナル・号・ページ | Nature, Vol. 565, Issue 7738, Page 192-197, Year 2019 |
掲載日 | 2018年12月31日 |
![]() | Guanghui Yang / Rui Zhou / Qiang Zhou / Xuefei Guo / Chuangye Yan / Meng Ke / Jianlin Lei / Yigong Shi / ![]() |
PubMed 要旨 | Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of ...Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase. |
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手法 | EM (単粒子) |
解像度 | 2.7 Å |
構造データ | |
化合物 | ![]() ChemComp-NAG: ![]() ChemComp-PC1: ![]() ChemComp-CLR: |
由来 |
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![]() | MEMBRANE PROTEIN / complex |