Lassa Virus Nucleoprotein:
The nucleocapsid protein of the Lassa virus is one of the key components of the viral structure and it is essential for the pathogenicity of the virus. The protein is the 1st protein expressed in infected cells and is the major structural element of the virus.The nucleoprotein encapsidates viral genomic RNAs forming ribonucleoprotein (RNP) complexes (Qi et al, 2010) and is also required for both RNA replication and transcription. Through an unknown mechanism, arenaviruses, such as the Lassa virus, are known to snatch the cap structure of cellular mRNAs to use as primers for viral transcription. In the acute cases of Lassa fever, the immune system is thought to suppressed by repression of type I interferon (IFN) induction. No mechanism is currently known however it has been proposed that the Lassa NP is actively involved.
Nucleoprotein Key Facts:
- The nucleoprotein (NP) monomer is comprised of 569 amino acid residues (n.b only 514 residues have been resolved in the latest crystal structure (Qi et al, 2010) )
- Mainly exists as a trimer but it can also exist as a hexamer
- The NP has two main domains; An N terminal domain characterized by residues 7-338 & a C terminal domain characterized by residues 364-561. A linker region connects these two domains.
- The protein has three main functions:
- Viral genomic RNA binding
- A 3'--5' exoribonuclease activity (C Domain) --> Immune Suppression
- 5' mRNA Cap Binding activity (N Domain) --> Viral Transcription
(Click on the images to enlarge)The PyMOL structures shown above illustrate the the 3D structure of both monomeric and trimeric Lassa nucleoprotein in both surface and cartoon views. The green regions represent the C-domain and the blue regions represent the N-domain. The Lassa NP exists as both a trimer and a hexamer, however no lab has been able to crystallise the hexamer so no structural data exists at this time. Links to appropriate structural entries can be found in the characterisation tab. The structures were obtained by X ray crystallography. For the exact crystallisation conditions see the methods (Qi et al 2010) section of the research articles.
The dimensions of the trimeric form of the nucleoprotein:
Figure 2: The dimensions of the LASV NP (trimer). The pore like structure found with the trimer has a diameter of 23Å. The longest and shortest lengths of the trimeric structure are 118Å and 98Å respectively. Image courtesy of Xiaoxuan et al 2010. Cap binding and Immune Evasion revealed by Lassa nucleoprotein strucutre. Supplementary Information Nature Vol 468 pg 12 Dec 2010The movie below shows the location of the two major active regions of the LASV NP (monomer):
The 3'--5' exonuclease region (red) found in the C domain (green) and the 5' mRNA cap binding region (3 seperate regions:orange, red and yellow) found in the N domain (blue). Viral genomic RNA binding is believed to take place in the groove between the two domains.
By Oliver Glass & Miles Glanfield
Looks very good. Well done, Mr Pymol! You should make all the backgrounds of figures identical like you told us ;)
ReplyDeleteThere is a lot of information in this blog, the pictures are very helpful to show what the text is explaining. Maybe a page with the key points from the paper or what you found most interesting would be helpful
ReplyDeleteThis blog looks very good! There are a couple of sections with lots of interesting information, although some are shorter. Maybe you could add some more info in those ones? Overall very good, though.
ReplyDeleteGood use of PyMOL, clearly proficiency in that art. Nice and informative, and I like the links in the references.
ReplyDeleteJust a couple of minor (not scientific) niggles:
-your "prime" symbols seem to be showing up as the code for the symbol rather than the symbol itself in your tabs.
-you may want to change 'a', 'b', and 'g' to α, β, and γ respectively in your cap binding page.
Otherwise, it's all good.