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The Mechanisms of Membrane Binding by the Autophagy Initiation Complex
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | The Mechanisms of Membrane Binding by the Autophagy Initiation Complex. |
| 개인저자 | Damasio, Alejandro. |
| 단체저자명 | Dartmouth College. Chemistry. |
| 발행사항 | [S.l.]: Dartmouth College., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 187 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781088390979 |
| 학위논문주기 | Thesis (Ph.D.)--Dartmouth College, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Ragusa, Michael J. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | Membrane binding proteins play a key role organelle structure and vesicle trafficking. In lysosomal degradation, membrane remodeling plays a crucial role in capturing and delivering the cargo to the lysosome to be degraded. In the cytosol, the main way to target cellular components to the lysosome is called autophagy. Autophagy is a catabolic process that helps deliver these protein aggregates and damaged organelles to the lysosome (or vacuole in yeast) in an efficient manner. As in other membrane remodeling processes, there are sets of proteins that are required for the function of the pathway. Atg20 and Atg24 are BAR-domain containing proteins that are required for selective autophagy in yeast. BAR domains are usually involved in sensing and inducing curvature in membrane, and while many BAR domain proteins have been studied in the past, these two remain unknown. To elucidate on the role of these two proteins in autophagy, we have investigated the structure and function of Atg20 and Atg24 using X-ray crystallography, Small-angle X-ray scattering, computational modeling, and biochemical assays. These two proteins are shown to form a non-canonical BAR heterodimer, which inherently causes asymmetry in the protein complex. This asymmetry proves to be important in the formation of smaller autophagosomes, which is one of the big differences between selective and non-selective autophagy.Atg13 is one of the most important subunits in the Atg1 initiation complex. In yeast, Atg13 domain architecture includes a long C-terminal intrinsically disordered region (IDR). This IDR has been shown to interact with a set of autophagy related proteins as well as membranes. Its membrane-binding region has not been well characterized, so we have explored this region's function by probing Atg13's membrane binding activity and its effect in Vac8 binding using liposome binding assays, isothermal titration calorimetry and cell assays. In this study, we show how the phospholipid motifs and the Vac8 binding interface are close in proximity and are mutually exclusive, demonstrating that the Atg13 IDR works as a hub between Vac8 and the expanding phagophore, and aiding the autophagy machinery to be at the correct location during autophagy initiation. |
| 일반주제명 | Biochemistry. |
| 언어 | 영어 |
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: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
