Clinical issue γ-secretase is a ubiquitous integral membrane multimolecular protease complex.
γ-secretase is a membrane-embedded protease complex consisting of presenilin 1 (PS1), nicastrin, anterior pharynx-defective 1, and presenilin enhancer 2 [13].
Previous studies suggested that the tetra-tricopeptide repeat domain 19 (TTC19) protein collaborates with an inner membrane protease SLP2-PARL-YME1L (SPY) complex to remove UQCRFS1N (residues 1 78 amino acids) from the full length UQCRFS1 after its incorporation into CIII (Bottani et al., 2017; Wai et al., 2016).
γ-Secretase is a multimeric protease complex that localizes at the plasma membrane and endosomes and generates the amyloid β (Aβ) peptide, the principal component of amyloid plaques in Alzheimer's disease (AD) [ 1, 2].
In the AD cascade, APP is cleaved initially by β-secretase (BACE), leaving the C99 fragment in the membrane, which is then cleaved by gamma-secretase, an aspartyl protease complex [ 4, 5].
Ligand binding induces a conformational change that allows the first proteolytic cut by "A Disintegrin And Metalloprotease," ADAM (the principal involved are 10 and 17) [ 31] which removes the extracellular portion of Notch and creates a membrane-tethered intermediate that is a substrate for γ-secretase, a cleaving protease complex.
The first cleavage occurs at a luminal, juxtamembrane position, resulting in the formation of a membrane-bound C-terminal stub that, in a subsequent step, is cleaved by an unconventional protease complex, called γ-secretase, within the transmembrane domain, thereby liberating Aβ.
That these receptors orchestrate protease signaling through PARs indicates potential immunomodulatory roles of protease complex signaling.
26S protease is a huge protease complex widely found in many organisms [ 24].
