Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface.
The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in...
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doaj-9e1ff19b6a9640b4a5e5eaf36d17d68b2020-11-25T01:53:29ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0198e100354910.1371/journal.ppat.1003549Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface.Guoliang LuPeng GongThe flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances.http://europepmc.org/articles/PMC3738499?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guoliang Lu Peng Gong |
spellingShingle |
Guoliang Lu Peng Gong Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. PLoS Pathogens |
author_facet |
Guoliang Lu Peng Gong |
author_sort |
Guoliang Lu |
title |
Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. |
title_short |
Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. |
title_full |
Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. |
title_fullStr |
Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. |
title_full_unstemmed |
Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a conserved methyltransferase-polymerase interface. |
title_sort |
crystal structure of the full-length japanese encephalitis virus ns5 reveals a conserved methyltransferase-polymerase interface. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2013-01-01 |
description |
The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. The structure completes the vision for polymerase motifs F and G, and depicts defined intra-molecular interactions between RdRP and MTase. Key hydrophobic residues in the RdRP-MTase interface are highly conserved in flaviviruses, indicating the biological relevance of the observed conformation. Our work paves the way for further dissection of the inter-regulations of the essential enzymatic activities of NS5 and exploration of possible other conformations of NS5 under different circumstances. |
url |
http://europepmc.org/articles/PMC3738499?pdf=render |
work_keys_str_mv |
AT guolianglu crystalstructureofthefulllengthjapaneseencephalitisvirusns5revealsaconservedmethyltransferasepolymeraseinterface AT penggong crystalstructureofthefulllengthjapaneseencephalitisvirusns5revealsaconservedmethyltransferasepolymeraseinterface |
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