title: A 1.55 A resolution X-ray crystal structure of HEF2/ERH and insights into its transcriptional and cell-cycle interaction networks.
abstract: Functional complementation screens can identify known or novel proteins with important intracellular activities. We have isolated human enhancer of filamentation 2 (HEF2) in a screen to find human genes that promote pseudohyphal growth in budding yeast. HEF2 is identical to enhancer of rudimentary homolog (ERH), a highly conserved protein of 104 amino acids. In silico protein-interaction mapping implies that HEF2/ERH interacts with transcription factors, cell-cycle regulators, and other proteins shown to enhance filamentous growth in S. cerevisiae, suggesting a context for studies of HEF2/ERH function. To provide a mechanistic basis to study of HEF2/ERH, we have determined the crystal structure of HEF2/ERH at 1.55 A. The crystal asymmetric unit contains a HEF2/ERH monomer. The two monomers of the physiological dimer are related by the y, x, -z crystal symmetric operation. The HEF2/ERH structure is characterized by a novel alpha + beta fold, a four-strand antiparallel beta-sheet with three alpha-helixes on one side of the sheet. The beta-sheets from the two monomers together constitute a pseudo-beta-barrel, and form the center of the functional HEF2/ERH dimer, with a cavity channel at the dimer interface. Docking of this structure to the HEF2/ERH partner protein DCOH/PCD suggests that HEF2/ERH may regulate the oligomeric state of this protein. These data suggest that HEF2/ERH may be an important transcription regulator that also functions in the control of cell-cycle progression.
authors: Department of Biology, Illinois Institute of Technology, Chicago, Illinois 60616, USA.
authors: Tengchuan
authors: T
authors: Jin
authors: Feng
authors: F
authors: Guo
authors: Ilya G
authors: IG
authors: Serebriiskii
authors: Andrew
authors: A
authors: Howard
authors: Yu-Zhu
authors: YZ
authors: Zhang
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division; D018360:Crystallography, X-Ray; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000166:cytology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; C484495:ERH protein, human; D014157:Transcription Factors