Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.

ABSTRACT: Intramembrane-cleaving proteases (I-CLiPs) activate pools of single-pass helical membrane protein signaling precursors that are key in the physiology of prokaryotic and eukaryotic cells. Proteases typically cleave peptide bonds within extended or flexible regions of their substrates, and thus the mechanism underlying the ability of I-CLiPs to hydrolyze the presumably α-helical transmembrane domain (TMD) of these membrane proteins is unclear. Using deep-ultraviolet resonance Raman spectroscopy in combination with isotopic labeling, we show that although predominantly in canonical α-helical conformation, the TMD of the established I-CLiP substrate Gurken displays 3₁₀-helical geometry. As measured by microscale thermophoresis, this substrate binds with high affinity to the I-CLiPs

SUBMITTER: Brown MC 

PROVIDER: S-EPMC5954294 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature