2024-03-28T10:41:02Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1100702023-02-06T14:01:31Zcom_10261_25com_10261_1com_10261_41col_10261_278col_10261_294
Activation mechanism of a noncanonical RNA-dependent RNA polymerase
Garriga, Damià
Navarro, Aitor
Querol-Audí, Jordi
Abaitua Elustondo, Fernando
Rodríguez Aguirre, José F.
Verdaguer, Núria
Noncanonical palm
Infectious bursal disease virus
Double-stranded RNA viruses
Virus evolution
Birnavirus replication
Two lineages of viral RNA-dependent RNA polymerases (RDRPs) differing in the organization (canonical vs. noncanonical) of the palm subdomain have been identified. Phylogenetic analyses indicate that both lineages diverged at a very early stage of the evolution of the enzyme [Gorbalenya AE, Pringle FM, Zeddam JL, Luke BT, Cameron CE, Kalmakoff J, Hanzlik TN, Gordon KH, Ward VK (2002) J Mol Biol 324:47-62]. Here, we report the x-ray structure of a noncanonical birnaviral RDRP, named VP1, in its free form, bound to Mg2+ ions, and bound to a peptide representing the polymerase-binding motif of the regulatory viral protein VP3. The structure of VP1 reveals that the noncanonical connectivity of the palm subdomain maintains the geometry of the catalytic residues found in canonical polymerases but results in a partial blocking of the active site cavity. The VP1-VP3 peptide complex shows a mode of polymerase activation in which VP3 binding promotes a conformational change that removes the steric blockade of the VP1 active site, facilitating the accommodation of the template and incoming nucleotides for catalysis. The striking structural similarities between birnavirus (dsRNA) and the positive-stranded RNA picornavirus and calicivirus RDRPs provide evidence supporting the existence of functional and evolutionary relationships between these two virus groups. © 2007 by The National Academy of Sciences of the USA.
This work was supported by Ministerio de Educacion y Ciencia Grants AGL2003-07189 (to J.F.R.) and BFU2005-02376/BMC (to N.V.). D.G. and J.Q.-A were supported by I3P contracts from Consejo Superior de Investigaciones Cientificas. Financial support was provided by the European Synchrotron Radiation Facility
Peer Reviewed
2015-02-02T13:51:56Z
2015-02-02T13:51:56Z
2007-12-18
2015-02-02T13:51:56Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1073/pnas.0704447104
issn: 0027-8424
Proceedings of the National Academy of Sciences of the United States of America 104(51): 20540-20545 (2007)
http://hdl.handle.net/10261/110070
10.1073/pnas.0704447104
18077388
http://dx.doi.org/10.1073/pnas.0704447104
none
National Academy of Sciences (U.S.)