A feasibility study on computational prediction on the death domain superfamily protein oligomers

Death Domain (DD) is one of the largest domain super-families, which comprises of the death domain(DD) subfamily, the death effector domain (DED) subfamily, the pyrin domain (PYD) subfamily, and the caspase recruitment domain (CARD) subfamily, that can lead to inflammatory response and cell death in...

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Main Author: Zhang, Jiawen
Other Authors: Wu Bin
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2020
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Online Access:https://hdl.handle.net/10356/144233
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1442332023-02-28T18:49:42Z A feasibility study on computational prediction on the death domain superfamily protein oligomers Zhang, Jiawen Wu Bin School of Biological Sciences wubin@ntu.edu.sg Science::Biological sciences Death Domain (DD) is one of the largest domain super-families, which comprises of the death domain(DD) subfamily, the death effector domain (DED) subfamily, the pyrin domain (PYD) subfamily, and the caspase recruitment domain (CARD) subfamily, that can lead to inflammatory response and cell death in innate immunity system. CARD-containing proteins are involved in processes relating to inflammation and apoptosis. The identity-defining step in this process is that the CARDs oligomerize into functional macromolecular protein complexes in a helical symmetry through direct interactions between individual CARDs motifs by mediating homotypic interaction. Computational predictions allow us to further characterise the mechanism of CARD:CARD interactions between different CARD-proteins. This computational work provides a framework to improve our understanding of death domain assembling oligomeric signalling complexes to direct innate immune and inflammatory responses.In order to investigate the signaling transduction process and validate our prediction and hypothesis, we conducted the structural study of the CARD8-CARD oligomeric complex by cryoEM. The CARD domain of CARD8 (CARD8-CARD) oligomerizes to form the filamentous structure in responses to upstream CARDs and activate Caspase1 to conduct the inflammatory response. We successfully resolved the structure of the filamentous CARD8-CARD complex with a resolution of 3.7Å(central segment). With the structure at near-atomic resolution, we managed to demonstrate the mechanism of CARD8-CARD crosstalk to upstream or downstream CARDs. Doctor of Philosophy 2020-10-22T01:18:47Z 2020-10-22T01:18:47Z 2020 Thesis-Doctor of Philosophy Zhang, J. (2020). A feasibility study on computational prediction on the death domain superfamily protein oligomers. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/144233 10.32657/10356/144233 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
spellingShingle Science::Biological sciences
Zhang, Jiawen
A feasibility study on computational prediction on the death domain superfamily protein oligomers
description Death Domain (DD) is one of the largest domain super-families, which comprises of the death domain(DD) subfamily, the death effector domain (DED) subfamily, the pyrin domain (PYD) subfamily, and the caspase recruitment domain (CARD) subfamily, that can lead to inflammatory response and cell death in innate immunity system. CARD-containing proteins are involved in processes relating to inflammation and apoptosis. The identity-defining step in this process is that the CARDs oligomerize into functional macromolecular protein complexes in a helical symmetry through direct interactions between individual CARDs motifs by mediating homotypic interaction. Computational predictions allow us to further characterise the mechanism of CARD:CARD interactions between different CARD-proteins. This computational work provides a framework to improve our understanding of death domain assembling oligomeric signalling complexes to direct innate immune and inflammatory responses.In order to investigate the signaling transduction process and validate our prediction and hypothesis, we conducted the structural study of the CARD8-CARD oligomeric complex by cryoEM. The CARD domain of CARD8 (CARD8-CARD) oligomerizes to form the filamentous structure in responses to upstream CARDs and activate Caspase1 to conduct the inflammatory response. We successfully resolved the structure of the filamentous CARD8-CARD complex with a resolution of 3.7Å(central segment). With the structure at near-atomic resolution, we managed to demonstrate the mechanism of CARD8-CARD crosstalk to upstream or downstream CARDs.
author2 Wu Bin
author_facet Wu Bin
Zhang, Jiawen
format Thesis-Doctor of Philosophy
author Zhang, Jiawen
author_sort Zhang, Jiawen
title A feasibility study on computational prediction on the death domain superfamily protein oligomers
title_short A feasibility study on computational prediction on the death domain superfamily protein oligomers
title_full A feasibility study on computational prediction on the death domain superfamily protein oligomers
title_fullStr A feasibility study on computational prediction on the death domain superfamily protein oligomers
title_full_unstemmed A feasibility study on computational prediction on the death domain superfamily protein oligomers
title_sort feasibility study on computational prediction on the death domain superfamily protein oligomers
publisher Nanyang Technological University
publishDate 2020
url https://hdl.handle.net/10356/144233
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