Purine
Global structure of the guanine riboswitch.
Binding of hypoxanthine to the three way junction (note that hypoxanthine is a soluble guanine analog that is normally found in cells).
Binding pocket of a dG-selective aptamer domain.
Electron density map of the binding pocket of a C74U mutant of the guanine riboswitch bound to 1,3,5-triaminopyrmidine (3APy).
PDB ID:
TheB. subtilis xpt-pbuX guanine riboswitch was the first X-ray structure of a natural aptamer. This landmark structure showed several features that were subsequently shown to be common amongst all of the riboswitches:
1. Nearly full encapsulation of the ligand, such that elements of the RNA structure were stabily formed through ligand binding.
2. Ligand binding was proposed to stabilize the "switching sequence" located on the 3'-side of the P1 helix. This sequence is mutually shared between the aptamer domain and expression platform. Incorporation of this sequence into the aptamer domain through ligand binding fates the mRNA to premature transcriptional termination.
3. Recognition of adenine is as simple as switching the identity of cytosine 74 to a uridine.
Binding of 2'-deoxyguanosine: PDB ID
Along with binding purine nucleobaes, a class of RNAs within the purine family can also bind purine ribonucleosides (specifically, 2'-deoxyguanosine, dG). Using a mutagenesis strategy, we found that the most critical residue for allowing dG recognition is a cytosine at position 51. Note that this residue shifts its position relative to U51 in the hypoxanthine bound structure to allow for the dexoxyribose sugar to be accommodated.
Binding of pyrimidines to the purine riboswitch: PDB ID
We have also discovered that certain pyrimidine compounds that can satisfy the hydrogen bonding arrangement of a purine can also bind to these aptamers.