Dokument: The effects of dimerization and membrane binding on protein dynamics: the cases of GABARAP and guanylate binding proteins

Titel:The effects of dimerization and membrane binding on protein dynamics: the cases of GABARAP and guanylate binding proteins
URL für Lesezeichen:
URN (NBN):urn:nbn:de:hbz:061-20221122-134449-9
Dokumententyp:Wissenschaftliche Abschlussarbeiten » Dissertation
Autor: Wang, Xue [Autor]
[Dateien anzeigen]Adobe PDF
[Details]11,90 MB in einer Datei
[ZIP-Datei erzeugen]
Dateien vom 22.11.2022 / geändert 22.11.2022
Beitragende:Jun.-Prof. Strodel, Birgit [Gutachter]
Prof. Dr. Willbold, Dieter [Gutachter]
Stichwörter:GABARAP, GBPs, MD simulation, Dimer, membrane binding protein
Dewey Dezimal-Klassifikation:500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie
Beschreibung:As an important part of the biological systems, proteins usually reply to specific cellular responses by binding to other biomolecules (lipids, carbohydrates, nucleic acids, and proteins) and act synergistically. To study the actions in more detail, in silico experiments were introduced years ago and form the basis of the current thesis. Apart from acting as monomers, proteins can self-associate to form dimers or higher-order oligomers. This homodimerization phenomenon is important for regulation and catalysis. Moreover, in addition to functioning in the cytoplasm, some proteins can bind to lipid membranes, as monomers or oligomers, or even act together with other proteins to function as membrane channels, promote membrane elongation/fusion, or damage the membrane. The exercise of these functions is closely related to the dynamics of the proteins. Two such proteins or protein classes are the gamma-aminobutyric acid receptor-associated protein (GABARAP) and guanylate binding proteins (GBPs), which are proteins known to oligomerize and bind to lipid membranes. GABARAP and two of the GBPs, namely the murine GBP2 and GBP7, are studied here using various in silico methods. First, since not all protein crystal structures have been resolved by experimental means, homology modeling methods were used to construct the unknown protein structures. Dimer structures of GABARAP and mGBP2 were also predicted based on the information available from previous experimental research. The structural dynamics and stabilities, including their monomer and dimer form, were then investigated using molecular dynamics simulations. Finally, the interplay between the proteins and lipid membranes following their membrane binding was studied, to gain more detailed information on the diversified roles that they play in the cell. The most relevant findings of this thesis work are: i) GABARAP seems to be a very stable protein with a limited degree of conformational flexibility, while mGBP2 and mGBP7 are very flexible exhibiting a large-scale hinge motion; ii) the dimer models that were constructed for GABARAP based on crystallographic data are not stable in solution, requiring more work to determine the GABARAP dimer structure; iii) GABARAP and mGBP2 bind very stably to lipid membranes via their lipid anchors while only few amino acid residues add to further protein-membrane interactions, and iv) membrane binding of mGBP7 is enabled via its C-terminal tail involving 49 amino-acid residues which was confirmed by experiments that were motivated by the current simulation results.
Lizenz:Creative Commons Lizenzvertrag
Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Fachbereich / Einrichtung:Mathematisch- Naturwissenschaftliche Fakultät
Dokument erstellt am:22.11.2022
Dateien geändert am:22.11.2022
Promotionsantrag am:29.09.2022
Datum der Promotion:26.10.2022
Status: Gast