6IDF

Cryo-EM structure of gamma secretase in complex with a Notch fragment

Summary for 6IDF

• Entry DOI: 10.2210/pdb6idf/pdb
• EMDB information: 3061 3237 3238 3239 3240 9648
• Descriptor: Nicastrin, CHOLESTEROL, Presenilin-1, ... (10 entities in total)
• Functional Keywords: complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 195623.20

Authors

Yang, G.,Zhou, R.,Zhou, Q.,Guo, X.,Yan, C.,Ke, M.,Lei, J.,Shi, Y. (deposition date: 2018-09-09, release date: 2018-12-26, Last modification date: 2025-04-09)

Primary citation

Yang, G.,Zhou, R.,Zhou, Q.,Guo, X.,Yan, C.,Ke, M.,Lei, J.,Shi, Y.
Structural basis of Notch recognition by human gamma-secretase
Nature, 565:192-197, 2019

PubMed Abstract: 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.

PubMed: 30598546
DOI: 10.1038/s41586-018-0813-8

Experimental method

ELECTRON MICROSCOPY (2.7 Å)