Dokument: The Interaction Network of Lipids, Peptides, and Receptors in Neuronal Processes
| Titel: | The Interaction Network of Lipids, Peptides, and Receptors in Neuronal Processes | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=54177 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20210921-084254-0 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Falke, Marcel [Autor] | |||||||
| Dateien: |
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| Beitragende: | Dr. Etzkorn, Manuel [Gutachter] Prof. Dr. Jaeger, Karl-Erich [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | A large number of cellular processes is regulated by a complex interplay between several hormones, membrane-embedded proteins and lipids. Especially G protein-coupled receptors (GPCRs) are one of the most essential classes of pharmacological targets and analysis of GPCR structure, function, and organization is one of the major challenges in molecular biology. Membrane biochemistry has benefited in the past from improvements both in terms of sample preparation (protein expression and purification) and biophysical characterization. However, finding a suitable membrane mimetic system for membrane protein stabilization as well as for
interaction studies with peptides remains still challenging. This work explores approaches to overcome these limitations as demonstrated for the GPCR melanocortin-4 receptor (MC4R) which is known to play an important role in energy homeostasis and most cases of monogenic obesity. Eukaryotic MC4R expression (human and insect cells) was established to enable insights into the dynamic processes of MC4R-hormone interactions. Contrary to previous reports, our data suggest that bone-derived hormone lipocalin 2 does not activate MC4R. With the aim to find a suitable membrane mimetic system for isolation of MC4R, we demonstrate detergent-free reconstitution of the receptor into styrene-maleic acid (SMA) lipid particles without removal from its native lipid environment. We further make use of the capability of the amphiphilic SMA copolymer to form lipid particles (SMALPs) out of synthetic lipids to characterize peptide-lipid interaction. In a similar way, we investigated the effect of membrane-binding on aggregation of the amyloidogenic peptide α-Synuclein (αSyn). We show that αSyn-lipid particles (αSyn-LiPs) are able to effectively induce, accelerate or inhibit αSyn aggregation emphasizing αSyn-LiPs as additional tool to study various aspects of αSyn amyloid fibril formation. Finally, we investigate interaction as well as binding modes of different epidermal growth factor receptor (EGFR) modulators in connection with nanodisc system enabling us to generate a network of possible EGFR modulators acting on the intracellular domain of the receptor. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie » Physikalische Biologie | |||||||
| Dokument erstellt am: | 21.09.2021 | |||||||
| Dateien geändert am: | 21.09.2021 | |||||||
| Promotionsantrag am: | 14.05.2020 | |||||||
| Datum der Promotion: | 17.07.2020 |
