Structural highlights
Function
[Q9PX50_9INFA] Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals and is responsible of the active RNP import into the nucleus through the cellular importin alpha/beta pathway. Later in the infection, nucleus export of RNP are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that the nucleoprotein binds directly exportin-1 (XPO1) and plays an active role in RNP nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmask nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus (By similarity).[SAAS:SAAS002141_004_603280]
Publication Abstract from PubMed
The threat of a pandemic outbreak of influenza virus A H5N1 has become a major concern worldwide. The nucleoprotein (NP) of the virus binds the RNA genome and acts as a key adaptor between the virus and the host cell. It, therefore, plays an important structural and functional role and represents an attractive drug target. Here, we report the 3.3-A crystal structure of H5N1 NP, which is composed of a head domain, a body domain, and a tail loop. Our structure resolves the important linker segments (residues 397-401, 429-437) that connect the tail loop with the remainder of the molecule and a flexible, basic loop (residues 73-91) located in an arginine-rich groove surrounding Arg150. Using surface plasmon resonance, we found the basic loop and arginine-rich groove, but mostly a protruding element containing Arg174 and Arg175, to be important in RNA binding by NP. We also used our crystal structure to build a ring-shaped assembly of nine NP subunits to model the miniribonucleoprotein particle previously visualized by electron microscopy. Our study of H5N1 NP provides insight into the oligomerization interface and the RNA-binding groove, which are attractive drug targets, and it identifies the epitopes that might be used for universal vaccine development.
Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design.,Ng AK, Zhang H, Tan K, Li Z, Liu JH, Chan PK, Li SM, Chan WY, Au SW, Joachimiak A, Walz T, Wang JH, Shaw PC FASEB J. 2008 Oct;22(10):3638-47. Epub 2008 Jul 9. PMID:18614582[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ng AK, Zhang H, Tan K, Li Z, Liu JH, Chan PK, Li SM, Chan WY, Au SW, Joachimiak A, Walz T, Wang JH, Shaw PC. Structure of the influenza virus A H5N1 nucleoprotein: implications for RNA binding, oligomerization, and vaccine design. FASEB J. 2008 Oct;22(10):3638-47. Epub 2008 Jul 9. PMID:18614582 doi:fj.08-112110
