PDBsum entry 2i4f

Transcription, cell cycle

PDB id

2i4f

Contents

			Protein chain

					100 a.a.

			Waters ×53

References listed in PDB file

Key reference

Title

A 1.55 a resolution X-Ray crystal structure of hef2/erh and insights into its transcriptional and cell-Cycle interaction networks.

Authors

T.Jin, F.Guo, I.G.Serebriiskii, A.Howard, Y.Z.Zhang.

Ref.

Proteins, 2007, 68, 427-437. [DOI no: 10.1002/prot.21343]

PubMed id

17444515

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 92%.

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.



	Figure 2. Figure 2. HEF2/ERH interacts with transcription factors and cell-cycle regulators. (A), recently identified interactions between mammalian HEF2/ERH and transcription factors.[31-37] Protein-protein interactions are shown by a connecting line with an arrowhead on each end. Interactions between enzyme-substrate pairs are indicated by an arrow pointing to the target. (B), an interaction network of HEF2/ERH Drosophila ortholog, e(r), compiled from interactions in the Drosophila Interactions Database (http://proteome.wayne.edu/PIMdb.html) using the IM Browser.[21] Node coloring was done manually using the IM Browser to indicate functions of corresponding proteins: green, transcription; red, cell cycle; yellow, other; and white, unknown function. Line coloring was done automatically by the IM Browser and indicate the source of the information on the interaction: blue, yeast two hybrid[38]; green, yeast two hybrid[39]; magenta, genetic interaction; cyan, supplemental prediction from C. elegans protein interactions; yellow, supplemental predictions from yeast protein interactions; and red, interaction indicated by more than one of the above sources.		Figure 4. Figure 4. Structure of the HEF2/ERH functional dimer. (A), a ribbon diagram of the HEF2/ERH dimer. The monomers (red and blue) are related by a twofold axis and can be generated by the y, x - z symmetric operation in the crystal lattice. (B), the -sheets from the monomers in the dimer form a pseudo- -barrel (generated by rotate 4A 90°C about the axis in the article and look-up ). There is no main chain-main chain hydrogen bond between strand 2 of the two monomers. Tyr79 of both monomers which contribute two hydrogen bonds (see text) are shown in ball-and-stick. C: a space-fill representation of the pseudo- -barrel, viewed from the bottom of the model in panel (B). The cavity channel at the interface of the two monomers is shown.

PROCHECK

	Headers