Crystal structure of ERA: A GTPase-dependent cell cycle regulator containing an RNA binding motif

ERA forms a unique family of GTPase. It is widely conserved and essential i n bacteria. ERI functions in cell cycle control by coupling cell division w ith growth rate, ERA homologues also are found in eukaryotes. Here we repor t the crystal structure of ERA from Escherichia coli. The structure has bee n determined at 2.4-Angstrom resolution. It reveals a tno domain arrangemen t of the molecule: an N-terminal domain that resembles p21 Ras and a C-term inal domain that is unique. Structure-based topological search of the C dom ain fails to reveal any meaningful match, although sequence analysis sugges ts that it contains a KH domain. KH domains are RNA binding motifs that usu ally occur in tandem repeats and exhibit low sequence similarity except for the well-conserved segment VIGxxGxxIK. We have identified a beta alpha alp ha beta fold that contains the VIGxxGxxIK sequence and is shared by the C d omain of ERA and the ECH domain. We propose that this beta alpha alpha beta fold is the RNA binding motif, the minimum structural requirement for RNA binding, ERA dimerizes in crystal. The dimer formation involves a significa ntly distorted switch II region, which may shed light on how ERA protein re gulates downstream events.