Dr. Claudia Muhle-Goll

Karlsruher Institut für Technologie



Project P8: Investigation of Molecular Dynamics of Substrate Transmembrane α-Helices by Solution and Solid-State NMR Spectroscopy


 

In this project, we investigate the structure and dynamics of transmembrane (TM) proteases’ substrates using a combination of solution and solid-state NMR spectroscopy. As the exact mechanism by which transmembrane proteases recognize their substrates is still not clear, we investigate if the molecular dynamics of a TM helix may determine its suitability as a substrate for intramembrane proteolysis.

 

To this end, we will apply numerous NMR techniques in solution and in membrane reconstituted systems. In close collaborations with the cell biology and computer simulation groups within the consortium this approach will shed more light on the mechanism by which transmembrane proteases recognize/bind and process their substrates.

 


Publications (FOR 2290)


 

Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.

Götz A, Mylonas N, Högel P, Silber M, Heinel H, Menig S, Vogel A, Feyrer H, Huster D, Luy B, Langosch D, Scharnagl C, Muhle-Goll C, Kamp F, Steiner H.

Biophys J. 2019 Jun 4;116(11):2103-2120. doi: 10.1016/j.bpj.2019.04.030. Epub 2019 May 3. PMID: 31130234

 

Increased H-Bond Stability Relates to Altered ε-Cleavage Efficiency and Aβ Levels in the I45T Familial Alzheimer's Disease Mutant of APP.

Götz A, Högel P, Silber M, Chaitoglou I, Luy B, Muhle-Goll C, Scharnagl C, Langosch D.

Sci Rep. 2019 Mar 29;9(1):5321. doi: 10.1038/s41598-019-41766-1. PMID: 30926830

 



Research Unit FOR 2290