Format

Send to

Choose Destination
Biochemistry. 2019 Jul 16;58(28):3065-3068. doi: 10.1021/acs.biochem.9b00505. Epub 2019 Jul 8.

Conformationally Flexible Sites within the Transmembrane Helices of Amyloid Precursor Protein and Notch1 Receptor.

Author information

1
Lehrstuhl Chemie der Biopolymere , Technische Universität München , Weihenstephaner Berg 3 , 85354 Freising , Germany.
2
Munich Center For Integrated Protein Science (CIPSM) , Munich Germany.

Abstract

Intramembrane proteases typically cleave multiple substrates within their transmembrane domains (TMDs). Because substrate TMDs lack a consensus sequence around their scissile sites, it remains unclear how the enzyme discriminates substrates from nonsubstrates at the level of their TMDs. Here, we compare the previously well investigated TMDs of γ-secretase substrates C99 and Notch1 in terms of helix flexibility. Our results reveal that the low-stability site neigboring a functionally relevant diglycine hinge of C99 has an equivalent in the Notch1 TMD. This suggests that the tetra-alanine motif of Notch1 also functions as a hinge which may facilitate its cleavage.

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center