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돌연변이를 가진 Toll-like-receptor의 구조와 기능의 컴퓨터적 분석
- Alternative Title
- Computational analysis of single and double mutations on TLR4 structure and function
- Author(s)
- 김송미
- Advisor
- 최상돈
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2016-02
- Language
- eng
- Keyword
- Toll-like-receptor
- Alternative Abstract
- Toll like receptors (TLRs) are important receptors on cell membrane that play a critical role in immune response. Among them, Toll like receptor 4 is involved in lipopolysaccharide detection from the Gram-negative bacteria. Once it sense the LPS in the medium, it initiates a signaling pathway to overcome bacterial intrusion. In order to perform its functions, TLR4 has to be in a stable dimeric form to allow the cytoplasmic domain to come close and dock properly. Although, different TLR4 in different species vary to different extent, two very particular mutations abrogate the stability of the complex that results in revocation of TLR4 signaling. These mutations, D299G and T399I, are in the ectodomain of TLR4, where it effects structural organization of TLR4. Crystallographic studies has given the valuable information regarding the structural aspects of the TLR4 ectodomain; however, what are the dynamical features that malfunction TLR4 are largely elusive. In this study, molecular dynamics simulations (MDS) have been performed to look into the structural parameters that alter due to these mutations. MDS revealed that the mutated ectodomains are fluctuating differently than that of wild type (WT). Root mean square fluctuations (RMSF) were different as well as number of hydrogen bonds. The distribution of phi, psi and omega were also distinctly variable in these complexes when measured around the mutated regions. In conclusion, this study substantially revealed the mutant-specific conformational alterations, which can lay further evidence that mutations of those residues that are not directly involved in protein-protein recognition or ligand binding can severely harm the complex formation.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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