Molecular Dynamics Activation of γ-Secretase for Cleavage of Notch1 Substrate
Hung N. Do,
Shweta R. Malvankar,
Michael S. Wolfe
et al.
Abstract:Abstractγ-Secretase is an intramembrane aspartyl protease complex which cleaves the transmembrane domain of over 150 peptide substrates, including amyloid precursor protein (APP) and the Notch family of receptors, via two conserved aspartates D257 and D385 in the Presenilin-1 (PS1) catalytic subunit. However, while the activation of γ-secretase for cleavage of APP has been widely studied, the cleavage of Notch by γ-secretase remains poorly explored. Here, we combined Gaussian accelerated Molecular Dynamics (Ga… Show more
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