The C-terminal region of Ge-1 presents conserved structural features required for P-body localization
Abstract
The removal of the 5′ cap structure by the DCP1–DCP2 decapping complex irreversibly commits eukaryotic mRNAs to degradation. In human cells, the interaction between DCP1 and DCP2 is bridged by the Ge-1 protein. Ge-1 contains an N-terminal WD40-repeat domain connected by a low-complexity region to a conserved C-terminal domain. It was reported that the C-terminal domain interacts with DCP2 and mediates Ge-1 oligomerization and P-body localization. To understand the molecular basis for these functions, we determined the three-dimensional crystal structure of the most conserved region of the Drosophila melanogaster Ge-1 C-terminal domain. The region adopts an all α-helical fold related to ARM- and HEAT-repeat proteins. Using structure-based mutants we identified an invariant surface residue affecting P-body localization. The conservation of critical surface and structural residues suggests that the C-terminal region adopts a similar fold with conserved functions in all members of the Ge-1 protein family.
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Footnotes
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↵3 Present addresses: Department of Molecular Cell Biology and Howard Hughes Medical Institute, University of California at Berkeley, 731 Stanley Hall, Berkeley, CA 94720-3220, USA;
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↵4 Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080, USA.
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Reprint requests to: Elena Conti, Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany; e-mail: conti{at}biochem.mpg.de; or Elisa Izaurralde, Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany; e-mail: elisa.izaurralde{at}tuebingen.mpg.de; fax: 49-70-71-601-1353.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1222908.
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- Received June 13, 2008.
- Accepted July 7, 2008.
- Copyright © 2008 RNA Society
