Dissertation/ Thesis
Probing the long-range coupling mechanism of respiratory complex I by multiscale computational modeling
| العنوان: | Probing the long-range coupling mechanism of respiratory complex I by multiscale computational modeling |
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| المؤلفون: | Djurabekova, Amina |
| المساهمون: | Helsingin yliopisto, matemaattis-luonnontieteellinen tiedekunta, Helsingfors universitet, matematisk-naturvetenskapliga fakulteten, University of Helsinki, Faculty of Science, Hummer, Gerhard, Sharma, Vivek |
| بيانات النشر: | Helsingin yliopisto Helsingfors universitet University of Helsinki |
| سنة النشر: | 2024 |
| المجموعة: | Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: | biophysics, Doctoral Programme in Materials Research and Nanoscience, Materiaalitutkimuksen ja nanotieteiden tohtoriohjelma, Doktorandprogrammet i materialforskning och nanovetenskap, 114 Fysiikka, 114 Fysik, 114 Physical sciences |
| الوصف: | The field of bioenergetics deals with the conversion of energy from food to a usable form for biological organisms, such as adenosine triphosphate (ATP). The largest percentage of ATP is catalyzed by ATP synthase, which utilizes proton motive force (PMF) across the inner mitochondrial membrane. The respiratory complex I (RCI), the first and the largest protein complex in the electron transport chain (ETC), contributes to about 40% of the total PMF across the inner mitochondrial membrane. This L-shaped protein complex is found across organisms that engage in aerobic respiration, from bacteria to fungi and animals. The mass of the complex is around 500 kDa, whereas mitochondrial RCI reaches 1 MDa, primarily due to tens of accessory subunits not found in bacterial complexes. The primary function of RCI is to transfer two electrons from NADH to a quinone (Q) molecule, which binds in a ∼35 Å long Q-tunnel at one end of the membrane arm of the enzyme. This redox reaction is coupled to pumping four protons at the other end of the membrane arm against the PMF. Several computationally predicted Q binding sites have been captured in structures, but no explicit agreement exists on their function. Moreover, it remains unclear whether any surface Q binding sites influence Q entry/exit to the RCI or the coupling mechanism. It is still unclear how the substrate protons required for the redox reaction of Q are recruited and transported from the bulk. What gating mechanisms does the enzyme employ to prevent premature proton transfer? Then, further away from the redox reaction, it is still unclear how protons move in the membrane arm and what gating mechanisms are put in place to allow protons to be pumped against the gradient. To completely understand the molecular mechanism of RCI, it is also imperative to know how it interacts with its surroundings and other protein complexes in the ETC. This thesis tackles the above questions using the multiscale modeling and computational approach combined with experiments. Classical ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf; fulltext |
| اللغة: | English |
| ردمك: | 978-952-84-0462-0 952-84-0462-6 |
| تدمد: | 2954-2898 2954-2952 |
| Relation: | Dissertationes Universitatis Helsingiensis; 7/2025; http://hdl.handle.net/10138/587845 |
| الاتاحة: | http://hdl.handle.net/10138/587845 |
| Rights: | Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty. ; This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited. ; Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden. |
| رقم الانضمام: | edsbas.8D972F55 |
| قاعدة البيانات: | BASE |
| ردمك: | 9789528404620 9528404626 |
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| تدمد: | 29542898 29542952 |