Cargando…

Crystal Structure of the Japanese Encephalitis Virus Capsid Protein

Japanese encephalitis (JE) is inflammation and swelling of the brain caused by the JE virus (JEV), a mosquito-borne member of the Flavivirus family. There are around 68,000 JE cases worldwide each year, many of which result in permanent brain damage and death. There is no specific treatment for JE....

Descripción completa

Detalles Bibliográficos
Autores principales: Poonsiri, Thanalai, Wright, Gareth S. A., Solomon, Tom, Antonyuk, Svetlana V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669762/
https://www.ncbi.nlm.nih.gov/pubmed/31284608
http://dx.doi.org/10.3390/v11070623
_version_ 1783440446937104384
author Poonsiri, Thanalai
Wright, Gareth S. A.
Solomon, Tom
Antonyuk, Svetlana V.
author_facet Poonsiri, Thanalai
Wright, Gareth S. A.
Solomon, Tom
Antonyuk, Svetlana V.
author_sort Poonsiri, Thanalai
collection PubMed
description Japanese encephalitis (JE) is inflammation and swelling of the brain caused by the JE virus (JEV), a mosquito-borne member of the Flavivirus family. There are around 68,000 JE cases worldwide each year, many of which result in permanent brain damage and death. There is no specific treatment for JE. Here we present the crystal structure of the JEV capsid protein, a potential drug target, at 1.98 Å, and compare it to other flavivirus capsid proteins. The JEV capsid has a helical secondary structure (α helixes 1–4) and a similar protein fold to the dengue virus (DENV), the West Nile virus (WNV), and the Zika virus (ZIKV) capsid proteins. It forms a homodimer by antiparallel pairing with another subunit (‘) through α-helix 1-1’, 2-2’, and 4-4’ interactions. This dimeric form is believed to be the building block of the nucleocapsid. The flexibility of the N-terminal α helix-1 allows the formation of closed and open conformations with possible functional importance. The basic C-terminal pairing of α4-4’ forms a coiled-coil-like structure, indicating possible nucleic acid binding functionality. However, a comparison with other nucleic acid interacting domains indicates that homodimerization would preclude binding. This is the first JEV capsid protein to be described and is an addition to the structural biology of the Flavivirus.
format Online
Article
Text
id pubmed-6669762
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-66697622019-08-08 Crystal Structure of the Japanese Encephalitis Virus Capsid Protein Poonsiri, Thanalai Wright, Gareth S. A. Solomon, Tom Antonyuk, Svetlana V. Viruses Communication Japanese encephalitis (JE) is inflammation and swelling of the brain caused by the JE virus (JEV), a mosquito-borne member of the Flavivirus family. There are around 68,000 JE cases worldwide each year, many of which result in permanent brain damage and death. There is no specific treatment for JE. Here we present the crystal structure of the JEV capsid protein, a potential drug target, at 1.98 Å, and compare it to other flavivirus capsid proteins. The JEV capsid has a helical secondary structure (α helixes 1–4) and a similar protein fold to the dengue virus (DENV), the West Nile virus (WNV), and the Zika virus (ZIKV) capsid proteins. It forms a homodimer by antiparallel pairing with another subunit (‘) through α-helix 1-1’, 2-2’, and 4-4’ interactions. This dimeric form is believed to be the building block of the nucleocapsid. The flexibility of the N-terminal α helix-1 allows the formation of closed and open conformations with possible functional importance. The basic C-terminal pairing of α4-4’ forms a coiled-coil-like structure, indicating possible nucleic acid binding functionality. However, a comparison with other nucleic acid interacting domains indicates that homodimerization would preclude binding. This is the first JEV capsid protein to be described and is an addition to the structural biology of the Flavivirus. MDPI 2019-07-06 /pmc/articles/PMC6669762/ /pubmed/31284608 http://dx.doi.org/10.3390/v11070623 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Poonsiri, Thanalai
Wright, Gareth S. A.
Solomon, Tom
Antonyuk, Svetlana V.
Crystal Structure of the Japanese Encephalitis Virus Capsid Protein
title Crystal Structure of the Japanese Encephalitis Virus Capsid Protein
title_full Crystal Structure of the Japanese Encephalitis Virus Capsid Protein
title_fullStr Crystal Structure of the Japanese Encephalitis Virus Capsid Protein
title_full_unstemmed Crystal Structure of the Japanese Encephalitis Virus Capsid Protein
title_short Crystal Structure of the Japanese Encephalitis Virus Capsid Protein
title_sort crystal structure of the japanese encephalitis virus capsid protein
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669762/
https://www.ncbi.nlm.nih.gov/pubmed/31284608
http://dx.doi.org/10.3390/v11070623
work_keys_str_mv AT poonsirithanalai crystalstructureofthejapaneseencephalitisviruscapsidprotein
AT wrightgarethsa crystalstructureofthejapaneseencephalitisviruscapsidprotein
AT solomontom crystalstructureofthejapaneseencephalitisviruscapsidprotein
AT antonyuksvetlanav crystalstructureofthejapaneseencephalitisviruscapsidprotein