Dokument: Structural insights into selective autophagy and cellular membrane remodeling
| Titel: | Structural insights into selective autophagy and cellular membrane remodeling | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=61558 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20250305-102238-0 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Mostafavi, Siavash [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Sachse, Carsten [Gutachter] Jun.-Prof. Dr. Schröder, Gunnar [Gutachter] | |||||||
| Stichwörter: | Autophagy | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | In autophagy, large cellular debris is captured and packaged into membrane bound cellular structures called autophagosomes, after which it is shuttled to the lysosome or vacuole, degraded, and recycled. First, I set out to understand how autophagy cargo is specifically recognized by cellular receptors. Therefore, I determined a structure of the full length human selective autophagy receptor p62/SQSTM1. Second, I wanted to understand the structural mechanisms of membrane remodeling, a necessary process for many cellular functions including autophagy. Therefore, I focused on the yeast ESCRT pathway machinery involved in many membrane processes of the cell including autophagy and how ESCRT-III core proteins interact with each other and with membranes. The work carried out in the first part of this thesis has produced a high-resolution structure of full-length p62/SQSTM1 and shows that the protein assembles into a tubular helical scaffold with substantial flexibility. The filaments show local and global flexibility and show open and closed forms. While only the PB1 domain is well-resolved, the other domains appear as blobs or nonspecific density present on the inside of the tube. Experiments with p62 binding partners show that despite being buried inside the tube, the other domains are still available for interaction. In addition, the individual monomers of the filament may be able to dissociate and reassociate within the helical assembly. The work in the second part of this thesis has produced the first known structures of membranes remodeled by a protein coat consisting of yeast ESCRT-III complex subunits. In total, seven structures of the core ESCRT-III proteins bound to membranes show that the proteins form a coat around membranes and remodel them into tubular assemblies, a critical step in the function of the ESCRT-III complex. Furthermore, the structures show that by the addition or removal of protein subunits in the helical lattice, membranes remodeled into tubular structures can be effectively constricted down a width of less than 300 Å. Together, the determined structures of p62/SQSTM1 and ESCRT-III provide structural examples of active helical assemblies that perform important tasks in membrane trafficking processes such as autophagy and endocytosis. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie | |||||||
| Dokument erstellt am: | 05.03.2025 | |||||||
| Dateien geändert am: | 05.03.2025 | |||||||
| Promotionsantrag am: | 31.08.2022 | |||||||
| Datum der Promotion: | 29.11.2022 |
