Structure and dynamics of amyloidgenic proteins
Fibril forming peptides and proteins are involved in many fatal diseases (Alzheimer’s, Parkinson’s, and Huntington’s). We investigate the structure and dynamics of such proteins at different states of the fibrillation process by different methods including solid-state NMR, fluorescence, electron microscopy, or X-ray diffraction. Especially with the use of 13C/15N labelled peptides for solid-state NMR, important information on a molecular level can be obtained.
Currently, we are studying mainly amyloid ß peptides with different modifications to gain insights in the physical basis of the fibrillation process.
These modifications include:
– artificial and natural point mutations
– switchable peptide domains
– truncation and pyroglutamate formation
By comparing the fibril form the modified peptide with the wild-type, we acquire a deeper understanding of the processes during fibrillation as a basis for the development of the diseases.
Key Papers:
Fränzl, M., Thalheim, T., Adler, J., Huster, D., Posseckardt, J., Mertig, M, Cichos, F. “Thermophoretic trap for single amyloid fibril and protein aggregation studies”. Nat. Methods 16 (2019) 611-614.
Korn, A., Adler, J., McLennan, S., Krueger, M., Surendran, D., Maiti, S., Huster, D. Amyloid β (1-40) toxicity depends on the molecular contact between phenylalanine 19 and leucine 34. ACS Chem. Neurosci. 9 (2018) 790-799.
Korn, A., Surendran, D., Krueger, M., Maiti, S., Huster, D. Ring structure modifications of phenylalanine 19 increase fibrillation kinectics and reduce toxicity of amyloid β (1-40). Chem. Comm. 54 (2018) 5430-5433.
Adler, J., Scheidt, H.A., Lemmnitzer, K., Krüger, M., Huster, D. N-terminal lipid conjugation leads to the formation of N-terminally extended fibrils. Phys. Chem. Chem. Phys. 19 (2017) 1839-1846.
Chandra, B., Korn, A., Maity, B.K., Adler, J., Rawat, A., Krueger, M., Huster, D., Maiti, S. Stereoisomers probe steric zippers in amyloid-ß. J. Phys. Chem B. 121 (2017) 1835-1842.
Scheidt, H.A., Adler, J., Zeitschel, U., Höfling, C., Korn, A., Krueger, M., Roßner, S, Huster, D. Pyroglutamate-modified amyloid β (11-40) fibrils are more toxic than wildtype fibrils but structurally very similar. Chemistry 23 (2017) 15834-15838.
Adler, J., Baumann, M., Voigt, B., Scheidt, H.A., Bhowmik, D., Häupl, T., Abel, B., Madhu, P.K., Balbach, J., Maiti, S., Huster, D. A detailed analysis of the morphology of the fibrils of selectively mutated amyloid ß (1-40). Chem. Phys. Chem. 17 (2016) 2744-2753
Scheidt, H.A., Adler, J., Krueger, M., Huster, D. Fibrils of truncated pyroglutamyl-modified Aß peptide exhibit a similar structure as wildtype mature Aß fibrils. Sci. Rep. 6 (2016) 33531.
Scheidt, H.A., Das, A., Korn, A., Krueger, M., Maiti, S., Huster, D. Structural characteristics of oligomers formed by pyroglutamate-modified amyloid ß peptides studied by solid-state NMR. Phys. Chem. Chem. Phys. 22 (2020) 16887-16895.
Team:
- Dr. Holger A. Scheidt
- Dr. Juliane Adler
- Dr. Benedikt Schwarze
- Alexander Korn
Collaborations:
- Prof. Dr. Sudipta Maiti, TIFR, Indien
- Prof. Dr. Perunthiruthy K. Madhu, TIFR Indien
- Dr. Martin Kürger, Universität Leipzig
- Dr. Sven Rothemund, Universität Leipzig
- Prof: Dr. Frank Cichos, Universität Leipzig