Dengue virus (DENV) nonstructural protein 5 (NS5) is composed of two globular 
domains separated by a 10-residue linker. The N-terminal domain participates in 
the synthesis of a mRNA cap 1 structure ((7Me)GpppA(2'OMe)) at the 5' end of the 
viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, 
and nucleoside-2'O-methyltransferase activities. The C-terminal domain is an 
RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although 
crystal structures of the two isolated domains have been obtained, there are no 
structural data for full-length NS5. It is also unclear whether the two NS5 
domains interact with each other to form a stable structure in which the 
relative orientation of the two domains is fixed. To investigate the structure 
and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray 
scattering experiments with the full-length protein. NS5 was found to be 
monomeric and well-folded under the conditions tested. The results of these 
experiments also suggest that NS5 adopts multiple conformations in solution, 
ranging from compact to more extended forms in which the two domains do not seem 
to interact with each other. We interpret the multiple conformations of NS5 
observed in solution as resulting from weak interactions between the two NS5 
domains and flexibility of the linker in the absence of other components of the 
replication complex.