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

• DOI: 10.1073/pnas.96.15.8396
• Publication Date: 2002-07-26T14:32:33Z
• Authors: Xin Chen; Donald L. Court; Xinhua Ji
• Keywords: Models, Molecular; Protein Folding; 0303 health sciences; Binding Sites; Escherichia coli Proteins; Cell Cycle; Membrane Proteins; RNA-Binding Proteins; Hydrogen Bonding; Nerve Tissue Proteins; Crystallography, X-Ray; Protein Structure, Secondary; GTP Phosphohydrolases; Fragile X Mental Retardation Protein; 03 medical and health sciences; Bacterial Proteins; GTP-Binding Proteins; Escherichia coli; ras Proteins; Dimerization

ERA forms a unique family of GTPase. It is widely conserved and essential in bacteria. ERA functions in cell cycle control by coupling cell division with growth rate. ERA homologues also are found in eukaryotes. Here we report the crystal structure of ERA from Escherichia coli . The structure has been determined at 2.4-Å resolution. It reveals a two-domain arrangement of the molecule: an N-terminal domain that resembles p21 Ras and a C-terminal domain that is unique. Structure-based topological search of the C domain fails to reveal any meaningful match, although sequence analysis suggests that it contains a KH domain. KH domains are RNA binding motifs that usually occur in tandem repeats and exhibit low sequence similarity except for the well-conserved segment VIGxxGxxIK. We have identified a βα α β fold that contains the VIGxxGxxIK sequence and is shared by the C domain of ERA and the KH domain. We propose that this βα α β fold is the RNA binding motif, the minimum structural requirement for RNA binding. ERA dimerizes in crystal. The dimer formation involves a significantly distorted switch II region, which may shed light on how ERA protein regulates downstream events.