Structure of the phylogenetically most conserved domain of SRP RNA

The signal recognition particle (SRP) is a phylogenetically conserved ribon ucleoprotein required for cotranslational targeting of proteins to the memb rane of the endoplasmic reticulum of the bacterial plasma membrane, Domain IV of SRP RNA consists of a short stem-loop structure with two internal loo ps that contain the most conserved nucleotides of the molecule, All known e ssential interactions of SRP occur in that moiety containing domain IV, The solution structure of a 43-nt RNA comprising the complete Escherichia coli domain IV was determined by multidimensional NMR and restrained molecular dynamics refinement. Our data confirm the previously determined rigid struc ture of a smaller subfragment containing the most conserved, symmetric inte rnal loop A (Schmitz et al,, Nat Struct Biol, 1999, 6:634-638), where all c onserved nucleotides are involved in nucleotide-specific structural interac tions. Asymmetric internal loop B provides a hinge in the RNA molecule; it is partially flexible, yet also uniquely structured, The longer strand of i nternal loop B extends the major groove by creating a ledge-like arrangemen t; for loop B however, there is no obvious structural role for the conserve d nucleotides, The structure of domain IV suggests that loop A is the initi al site for the RNA/protein interaction creating specificity, whereas loop B provides a secondary interaction site.