Abstract: |
We report on the solution structure of an unprecedented intramolecular G-quadruplex formed by the guanosine-rich human chl1 intronic d(G3-N-G4-N2-G4-N-G3-N) 19-mer sequence in K+-containing solution. This G-quadruplex, composed of three stacked G-tetrads containing four syn guanines, represents a new folding topology with two unique conformational features. The first guanosine is positioned within the central G-tetrad, in contrast to all previous structures of unimolecular G-quadruplexes, where the first guanosine is part of an outermost G-tetrad. In addition, a V-shaped loop, spanning three G-tetrad planes, contains no bridging nucleotides. The G-quadruplex scaffold is stabilized by a T•G•A triple stacked over the G-tetrad at one end and an unpaired guanosine stacked over the G-tetrad at the other end. Finally, the chl1 intronic DNA G-quadruplex scaffold contains a guanosine base intercalated between an extended G-G step, a feature observed in common with the catalytic site of group I introns. This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to intronic G-quadruplex platforms. © 2010 Elsevier Ltd. All rights reserved. |