Frustration analysis of coronaviruses E protein variants in pentameric conformation

COVID-19 pandemic has spurred significant interest in studying coronavirus (CoV) protein design, infection process, and novel therapeutic targets. E protein is vital in coronavirus production and assembly and can potentially be a drug target through its ability to oligomerize and generate a pentamer...

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Main Author: Koh, Hui Fen
Other Authors: Konstantin Pervushin
Format: Final Year Project
Language:English
Published: Nanyang Technological University 2023
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Online Access:https://hdl.handle.net/10356/167176
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spelling sg-ntu-dr.10356-1671762023-05-29T15:33:11Z Frustration analysis of coronaviruses E protein variants in pentameric conformation Koh, Hui Fen Konstantin Pervushin School of Biological Sciences KPervushin@ntu.edu.sg Science::Biological sciences COVID-19 pandemic has spurred significant interest in studying coronavirus (CoV) protein design, infection process, and novel therapeutic targets. E protein is vital in coronavirus production and assembly and can potentially be a drug target through its ability to oligomerize and generate a pentameric ion channel (IC) in SARS-CoV-2. However, it is unclear if all Coronaviridae E protein homologs have this structural feature. Moreover, a recent hypothesis suggests that E protein may drive membrane remodeling through amyloid formation at the C-terminus. Thus, comparative analysis of E protein sequences from different CoV genera in this study aims to determine whether E protein across CoVs form a pentameric IC and identify critical amino acids in E protein’s transmembrane domain for oligomerization and IC formation may shed some light on these competing views. The stability analysis of representative sequences from each genus using Frustratometer Server suggests that Beta genus is the most stable in a pentameric conformation, followed by Alpha, Gamma and Delta. This finding offers new insights for future research on CoV sequence variations and structural experiments and suggests that some amino acid sequence variants from Delta genera may be incompatible with the canonical model of pentameric IC determined for SARS-CoV-2 E protein. Bachelor of Science in Biological Sciences 2023-05-24T05:18:30Z 2023-05-24T05:18:30Z 2023 Final Year Project (FYP) Koh, H. F. (2023). Frustration analysis of coronaviruses E protein variants in pentameric conformation. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/167176 https://hdl.handle.net/10356/167176 en 04MNP002679 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
Koh, Hui Fen
Frustration analysis of coronaviruses E protein variants in pentameric conformation
description COVID-19 pandemic has spurred significant interest in studying coronavirus (CoV) protein design, infection process, and novel therapeutic targets. E protein is vital in coronavirus production and assembly and can potentially be a drug target through its ability to oligomerize and generate a pentameric ion channel (IC) in SARS-CoV-2. However, it is unclear if all Coronaviridae E protein homologs have this structural feature. Moreover, a recent hypothesis suggests that E protein may drive membrane remodeling through amyloid formation at the C-terminus. Thus, comparative analysis of E protein sequences from different CoV genera in this study aims to determine whether E protein across CoVs form a pentameric IC and identify critical amino acids in E protein’s transmembrane domain for oligomerization and IC formation may shed some light on these competing views. The stability analysis of representative sequences from each genus using Frustratometer Server suggests that Beta genus is the most stable in a pentameric conformation, followed by Alpha, Gamma and Delta. This finding offers new insights for future research on CoV sequence variations and structural experiments and suggests that some amino acid sequence variants from Delta genera may be incompatible with the canonical model of pentameric IC determined for SARS-CoV-2 E protein.
author2 Konstantin Pervushin
author_facet Konstantin Pervushin
Koh, Hui Fen
format Final Year Project
author Koh, Hui Fen
author_sort Koh, Hui Fen
title Frustration analysis of coronaviruses E protein variants in pentameric conformation
title_short Frustration analysis of coronaviruses E protein variants in pentameric conformation
title_full Frustration analysis of coronaviruses E protein variants in pentameric conformation
title_fullStr Frustration analysis of coronaviruses E protein variants in pentameric conformation
title_full_unstemmed Frustration analysis of coronaviruses E protein variants in pentameric conformation
title_sort frustration analysis of coronaviruses e protein variants in pentameric conformation
publisher Nanyang Technological University
publishDate 2023
url https://hdl.handle.net/10356/167176
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