Sandbox WWC8
From Proteopedia
Contents |
Nucleoprotein of Influenza A
|
Introduction
Viruses with anti-sense RNA genomes, such as the influenza virus carry three core polypeptides inside their viral capsids in order to successfully enter a host and initiate the viral replication cycle. Especially important for viral replication and coordination with the host cell's replication machinery is a protein able to bind single-strand RNA scripts (ssRNA), forming ribonucleoprotein complexes (RNPs). This protein is commonly referred to as nucleoprotein (NP). The NP binds and transports viral RNA scripts to and from the host cell nucleus for transcription, replication, and packaging into new virions. When NP binds RNA, it is structure specific but not sequence specific, meaning NP will bind only ssRNA but will bind any ss-RNA script, viral or non-viral. Beyond the transport function, NP is an essential mediator between host and virus and coordinates complex processes during viral replication [1]. Due to its important function, NP is intensively studies as a potential drug target for antiviral pharmaceuticals [2].
Structural Features
The NP is a homo 3-mer - A3 with 499 amino acid residues. Each homomer provides a binding site for the viral RNA script. The homomers fold into a crescent shape with a head and a body domain, where the grove between the two domains hosts the ssRNA binding site on the outer surface of the homomer. INSERT IMAGE OF MONOMER AND MARKET BINDING SITE WITH COLORED DOMAINS HERE
Characterization of Possible Binding Interactions
Role of NP in the Viral Replication cycle
Identification of Antiviral Drug Targets on NP
SHOW INTERACTIVE IMAGE HERE FOR DEFINITION OF RNA BINDING GROOVE RESEARCH WITH NAPROXEN
OTHER POTENTIAL DRUG TARGETS: DISTURBING OLIGOMERIZATION AND NP-POLYMERASE INTERACTION
References
[1] A. Portela, P. Digard, The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication, Journal of General Virology. 83 (2002) 723–734. doi:10.1099/0022-1317-83-4-723.
[2] R.M. Krug, J.M. Aramini, Emerging antiviral targets for influenza A virus, Trends in Pharmacological Sciences. 30 (2009) 269–277. doi:10.1016/j.tips.2009.03.002.
