St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • Chemistry (School of)
  • Chemistry
  • Chemistry Theses
  • View Item
  •   St Andrews Research Repository
  • Chemistry (School of)
  • Chemistry
  • Chemistry Theses
  • View Item
  •   St Andrews Research Repository
  • Chemistry (School of)
  • Chemistry
  • Chemistry Theses
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Structural basis of Lassa fever nucleoprotein binding pathogen-associated pattern molecule dsRNA

Thumbnail
View/Open
XueJiangMPhilThesis.pdf (42.58Mb)
Date
30/11/2012
Author
Jiang, Xue
Supervisor
Dong, Changjiang
Keywords
Lassa fever virus
Nucleoprotein
Metadata
Show full item record
Altmetrics Handle Statistics
Abstract
Lassa fever virus (LASV) infects thousands of people and produces more than 5,000 deaths each year in West Africa. This severe virus is a huge threat, as it transmits between human and rodents, and no effective vaccine or drug is available currently. One key of getting control of this disease lies in the nucleoprotein (NP) of LASV, which plays an essential role in viral replication, transcription and immune suppression. The full length NP crystal structure has been solved, showing a novel structural fold and multi-functions with unusual mechanisms in immune suppression and viral RNA transcription. The C-terminal domain of LAVS NP is a 3’-5’ exonuclease, whose activity is essential for viral immune suppression. This domain alone can suppress an immune response and can degrade dsRNAs with specific preference higher than for ssRNAs. However, the detail of the mechanism is unclear. To understand the mechanism while avoiding another domain’s effect (the N-terminal domain), the C-terminal domain of LASV NP was expressed and purified, and pathogen-associated pattern molecular RNAs were synthesized chemically and biologically to carry on crystallization and functional testing. The C-domain crystals in complex with a pathogen-associated pattern molecule, triphosphate 8 nucleotide dsRNA were obtained. The crystal belongs to the space group P3 with unit cell dimension a=b=177.6 Å, c=56.49Å, α =β=90°, γ=120°. This crystal structure showed that the dsRNA binds in the 3’-5’ exonuclease active site with one 3’ end of the dsRNA perfectly sitting for cleavage. We are trying to figure out the detailed mechanism by mutagenesis, fluorescence-labeled RNA gel scan and band shift assays.
Type
Thesis, MPhil Master of Philosophy
Collections
  • Chemistry Theses
URI
http://hdl.handle.net/10023/3512

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter