Crystal structure of an enhancer of rudimentary homolog (ERH) at 2.1 Å resolution

The enhancer of rudimentary; gene, e(r), of Drosophila melanogaster encodes an enhancer of rudimentary (ER) protein with functions implicated in pyrimidine biosynthesis and the cell cycle. The ER homolog (ERH) is highly conserved among vertebrates, invertebrates, and plants. Xenopus laevis ERH was reported to be a transcriptional repressor. Here we report the 2.1 angstrom crystal structure of murine ERH (Protein Data Bank ID 1WZ7), determined by the multiwavelength anomalous dispersion (MAD) method. The monomeric structure of ERH comprises a single domain consisting of three alpha-helices and four P-strands, which is a novel fold. In the crystal structure, ERH assumes a dimeric structure, through interactions between the P-sheet regions. The formation of an ERH dimer is consistent with the results of analytical ultracentrifugation. The residues at the core region and at the dimer interface are highly conserved, suggesting the conservation of the dimer formation as well as the monomer fold. The long flexible loop (44 similar to 53) is also significantly conserved, suggesting that this loop region may be important for the functions of ERH. In addition, the putative phosphorylation sites are located at the start of the beta 2-strand (Thr18) and at the start of the alpha 1-helix (Ser-24), implying that the phosphorylation might cause some structural changes.