Solution structure of a unique G-quadruplex scaffold adopted by a guanosine-rich human intronic sequence.
We report on the solution structure of an unprecedented intramolecular G-quadruplex formed by the guanosine-rich human chl1 intronic d(G(3)-N-G(4)-N(2)-G(4)-N-G(3)-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.
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Vitaly
V
Kuryavyi
Dinshaw J
DJ
Patel
D001483:Base Sequence; D020134:Catalytic Domain; D054856:G-Quadruplexes; D006151:Guanosine / Q000737:chemistry*; D006801:Humans; D007438:Introns; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000235:genetics
D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D006151:Guanosine