@article{PAR00006537,
  title = {{R}ecognition of {RNA} cap in the {W}esselsbron {V}irus n{S}5 methyltransferase domain : implications for {RNA}-capping mechanisms in {F}lavivirus},
  author = {{B}ollati, {M}. and {M}ilani, {M}. and {M}astrangelo, {E}. and {R}icagno, {S}. and {T}edeschi, {G}. and {N}onnis, {S}. and {D}ecroly, {E}. and {S}elisko, {B}. and de {L}amballerie, {X}avier and {C}outard, {B}. and {C}anard, {B}. and {B}olognesi, {M}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he m{RNA}-capping process starts with the conversion of a 5'-triphosphate end into a 5'-diphosphate by an {RNA} triphosphatase, followed by the addition of a guanosine monophosphate unit in a 5'-5' phosphodiester bond by a guanylyltransferase. {M}ethyltransferases are involved in the third step of the process, transferring a methyl group from {S}-adenosyl-{L}-methionine to {N}7-guanine (cap 0) and to the ribose 2'{OH} group (cap 1) of the first {RNA} nucleotide; capping is essential for m{RNA} stability and proper replication. {I}n the genus {F}lavivirus, {N}7-methyltransferase and 2'{O}-methyltransferase activities have been recently associated with the {N}-terminal domain of the viral {NS}5 protein. {I}n order to further characterize the series of enzymatic reactions that support capping, we analyzed the crystal structures of {W}esselsbron virus methyltransferase in complex with the {S}-adenosyl-{L}-methionine cofactor, {S}-adenosyl-{L}-homocysteine (the product of the methylation reaction), {S}inefungin (a molecular analogue of the enzyme cofactor), and three different cap analogues ({G}ppp{G}, ({N}7{M}e){G}ppp{G}, and ({N}7{M}e){G}ppp{A}). {T}he structural results, together with those on other flaviviral methyltransferases, show that the capped {RNA} analogues all bind to an {RNA} high-affinity binding site. {H}owever, lack of specific interactions between the enzyme and the first nucleotide of the {RNA} chain suggests the requirement of a minimal number of nucleotides following the cap to strengthen protein/{RNA} interaction. {O}ur data also show that, following incubation with guanosine triphosphate, {W}esselsbron virus methyltransferase displays a guanosine monophosphate molecule covalently bound to residue {L}ys28, hinting at possible implications for the transfer of a guanine group to pp{RNA}. {T}he structures of the {W}esselsbron virus methyltransferase complexes obtained are discussed in the context of a model for {N}7-methyltransferase and 2'{O}-methyltransferase activities.},
  keywords = {{F}lavivirus ; {RNA} capping ; methyltransferase ; guanylyltransferase ; viral ; enzyme structure},
  booktitle = {},
  journal = {{J}ournal of {M}olecular {B}iology},
  volume = {385},
  numero = {1},
  pages = {140--152},
  ISSN = {0022-2836},
  year = {2009},
  DOI = {10.1016/j.jmb.2008.10.028},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00006537},
}