Biochemical and Structural Evidence in Support of a Coherent Model for the Formation of the Double-Helical Influenza A Virus Ribonucleoprotein
| dc.citation.firstpage | e00467 | |
| dc.citation.issueNumber | 1 | |
| dc.citation.journalTitle | mBio | |
| dc.citation.volumeNumber | 4 | |
| dc.contributor.author | Ye, Qiaozhen | |
| dc.contributor.author | Guu, Tom S.Y. | |
| dc.contributor.author | Mata, Dougslas A. | |
| dc.contributor.author | Kuo, Rei-Lin | |
| dc.contributor.author | Smith, Bartram | |
| dc.contributor.author | Krug, Robert M. | |
| dc.contributor.author | Tao, Yizhi Jane | |
| dc.date.accessioned | 2013-01-09T16:53:12Z | |
| dc.date.available | 2013-01-09T16:53:12Z | |
| dc.date.issued | 2012 | |
| dc.description.abstract | Influenza A virions contain eight ribonucleoproteins (RNPs), each comprised of a negative-strand viral RNA, the viral polymerase, and multiple nucleoproteins (NPs) that coat the viral RNA. NP oligomerization along the viral RNA is mediated largely by a 28-amino-acid tail loop. Influenza viral RNPs, which serve as the templates for viral RNA synthesis in the nuclei of infected cells, are not linear but rather are organized in hairpin-like double-helical structures. Here we present results that strongly support a coherent model for the assembly of the double-helical influenza virus RNP structure. First, we show that NP self-associates much more weakly in the absence of RNA than in its presence, indicating that oligomerization is very limited in the cytoplasm. We also show that once NP has oligomerized, it can dissociate in the absence of bound RNA, but only at a very slow rate, indicating that the NP scaffold remains intact when viral RNA dissociates from NPs to interact with the polymerase during viral RNA synthesis. In addition, we identify a previously unknown NP-NP interface that is likely responsible for organizing the double-helical viral RNP structure. This identification stemmed from our observation that NP lacking the oligomerization tail loop forms monomers and dimers. We determined the crystal structure of this NP dimer, which reveals this new NP-NP interface. Mutation of residues that disrupt this dimer interface does not affect oligomerization of NPs containing the tail loop but does inactivate the ability of NPs containing the tail loop to support viral RNA synthesis in minigenome assays. | |
| dc.embargo.terms | none | |
| dc.identifier.citation | Ye, Qiaozhen, Guu, Tom S.Y., Mata, Dougslas A., et al.. "Biochemical and Structural Evidence in Support of a Coherent Model for the Formation of the Double-Helical Influenza A Virus Ribonucleoprotein." <i>mBio,</i> 4, no. 1 (2012) American Society for Microbiology: e00467. http://dx.doi.org/10.1128/mBio.00467-12. | |
| dc.identifier.doi | http://dx.doi.org/10.1128/mBio.00467-12 | |
| dc.identifier.uri | https://hdl.handle.net/1911/68516 | |
| dc.language.iso | eng | |
| dc.publisher | American Society for Microbiology | |
| dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
| dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/3.0/ | |
| dc.title | Biochemical and Structural Evidence in Support of a Coherent Model for the Formation of the Double-Helical Influenza A Virus Ribonucleoprotein | |
| dc.type | Journal article | |
| dc.type.dcmi | Text | |
| dc.type.publication | publisher version |