Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/113010
Title: On the molecular organization of a succinyl-CoA-producing cell-free system : a cryo-EM and computational approach
Author(s): Skalidis, IoannisLook up in the Integrated Authority File of the German National Library
Referee(s): Kastritis, Panagiotis L.Look up in the Integrated Authority File of the German National Library
Stubbs, Milton
Tampé, RobertLook up in the Integrated Authority File of the German National Library
Granting Institution: Martin Luther University Halle-Wittenberg
Issue Date: 2023
Extent: 1 Online-Ressource (XII, 150, xliii Seiten)
Type: HochschulschriftLook up in the Integrated Authority File of the German National Library
Type: PhDThesis
Exam Date: 2023-06-16
Language: English
URN: urn:nbn:de:gbv:3:4-1981185920-1149670
Abstract: Metabolites play multifaceted roles in cellular communication, inflammation, and malignancy. Large enzymatic complexes called metabolons regulate metabolite availability, controlling critical aspects of cellular fate. To understand these assemblies, a native, fractionated extract derived from a cell-free system can be used. Cryogenic electron microscopy, complemented by biochemical assays, proteomics, and AI-based predictions, can visualize and interpret their structures. This thesis aims to elucidate protein community members and further analyzes the 2-oxoglutarate dehydrogenase complex. It reveals its structural features, kinetic characterization of its enzymatic reactions, and the role of the E3BPo subunit in its assembly. Integrative modeling provides insights into electrostatic interactions, flexible region stabilization, and tethering of peripheral subunits. The proposed model encompasses the structure and function of the oxoglutarate dehydrogenase complex in a cell-free system.
Metaboliten spielen vielseitige Rollen, beeinflussen zelluläre Kommunikation, Entzündungen und Malignität. Metabolons, große enzymatische Komplexe, regulieren Metabolitverfügbarkeit und kontrollieren zentrale Aspekte zell. Programmierung. Um diese Strukturen zu verstehen, kann ein natives, fraktioniertes Extrakt, in Form eines zellfreien Systems, verwendet werden. Kryo-Elektronenmikroskopie, biochemische Assays, Proteomik und KI-basierte Vorhersagen ermöglichen Strukturvisualisierung und -interpretation. Diese Arbeit fokussiert sich auf Proteinverbände wie den Oxoglutarat-Dehydrogenase-Komplex (OGDHc). Sie enthüllt Strukturmerkmale, kinetische Charakterisierung enzymatischer Reaktionen und die Rolle der E3BPo-Untereinheit bei der Assemblierung. Integrative Modellierung erlaubt Einblicke in elektrostatische Wechselwirkungen, Stabilisierung des flexiblen Bereichs und Verankerung peripherer Untereinheiten. Das Modell umfasst die Struktur und Funktion des OGDHc in einem zellfreien System.
URI: https://opendata.uni-halle.de//handle/1981185920/114967
http://dx.doi.org/10.25673/113010
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
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