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Molecular Metamorphosis in Transcriptional Regulation
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- Lüking, Malin, 1993- (författare)
- Uppsala universitet,Molekylär systembiologi,Uppsala University,Elf
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- Elf, Johan, Professor (preses)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär systembiologi
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- Muñoz, Victor, Professor (opponent)
- UC Merced, Protein Biophysics and Bioengineering
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(creator_code:org_t)
- ISBN 9789151318820
- Uppsala : Acta Universitatis Upsaliensis, 2023
- Engelska 73 s.
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Serie: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1651-6214 ; 2299
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Abstract
Ämnesord
Stäng
- The foundation of all life is the interaction of molecules. Molecular interaction occurs in the tightly packed cytoplasm. In this crowded environment, the molecules need to be able to establish stable interactions with specific interaction partners, and with specific ones only. Selectivity is essential for transcriptional regulation where DNA-binding proteins, more specifically transcription factors, need to reach their respective target DNA, such as an operator sequence, quickly. The transcription factor LacI for example reaches its DNA operator within minutes and establishes a tight interaction to it that will block transcriptions of the genes it regulates. With the other millions of sequences in the bacterial chromosome, it interacts only fleetingly. This is possible because a small part of the protein is disordered during the transient interaction with non-operator DNA. Only with specific DNA will the folding of the disordered region into a rigid helix be favored. When the disordered region folds into a helix, the transcription factor changes its structure and, with it, its function from a weak DNA binder to a strong one. Thinking about molecular structures as dynamic entities that react to their environment and understanding the origins of structural metamorphosis allow us to predict changes in the protein sequence that will affect their behavior in the cellular context. This is demonstrated in this thesis where I study the structural dynamics of LacI with molecular dynamic simulations and use the insights from these simulations to design protein variants with changed binding stability and selectivity.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Nyckelord
- Protein-DNA interactions
- Facilitated diffusion
- Binding Kinetics
- Molecular Simulations
- Fluorescence Microscopy
- Biology with specialization in Structural Biology
- Biologi med inriktning mot strukturbiologi
- Biology with specialization in Molecular Biotechnology
- Biologi med inriktning mot molekylär bioteknik
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)