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Crystal structures of ribosome anti-association factor IF6

Nature Structural Biology volume 7, pages 1156–1164 (2000)Cite this article

Abstract

Ribosome anti-association factor eIF6 (originally named according to translation initiation terminology as eukaryotic initiation factor 6) binds to the large ribosomal subunit, thereby preventing inappropriate interactions with the small subunit during initiation of protein synthesis. We have determined the X-ray structures of two IF6 homologs, Methanococcus jannaschii archaeal aIF6 and Sacchromyces cerevisiae eIF6, revealing a phylogenetically conserved 25 kDa protein consisting of five quasi identical α/β subdomains arrayed about a five-fold axis of pseudosymmetry. Yeast eIF6 prevents ribosomal subunit association. Comparative protein structure modeling with other known archaeal and eukaryotic homologs demonstrated the presence of two conserved surface regions, one or both of which may bind the large ribosomal subunit.

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Figure 1: eIF6 and aIF6 sequence alignments.
Figure 2: Yeast eIF6(1–224) prevents association of yeast ribosomal subunit.
Figure 3: Stereoview of the experimental electron density for one M. jannaschii aIF6 subdomain.
Figure 4: Pentein structures of aIF6 and eIF6.
Figure 5: Two perpendicular views of aIF6 subdomain B.
Figure 6: Sequence alignments of the M. jannaschii aIF6 subdomains.
Figure 7: Molecular surfaces of aIF6 and eIF6.
Figure 8: Perpendicular views of the water-filled hollow of aIF6.

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Acknowledgements

At the Brookhaven National Laboratory National Synchrotron Light Source, we thank Z. Dauter and K. R. Rajashankar for their help using beamline X9B. We thank G. Blobel, J. Bonanno, B.T. Chait, M.R. Chance, J. DeAngelis, R.C. Deo, M. Henderson, V. Ilyin, D. Jeruzalmi, J. Kuriyan, C. Kielkopf, C. Lima, J. Marcotrigiano, F. Melo, S. Nair, U. Pieper, G.A. Petsko, S.S. Ray, R. Sanchez, L. Shapiro, F.W. Studier, S. Swaminathan, R.M. Sweet, and W.B. Whitman for many useful discussions. We thank G. He for technical help and T. Niven for editorial assistance. S.K.B. is a member of the Howard Hughes Medical Institute. This work was supported by National Institutes of Health Grants (S.K.B. and A.S.), and by The Rockefeller University (C.M.G.). A.S. is an Alfred P. Sloan Research Fellow and an Irma T. Hirschl Trust Career Scientist, and is also support by The Merck Genome Research Institute, G. Harold and Leila Y. Mathers Charitable Foundation, and the National Science Foundation.

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  1. Roland Beckmann

    Present address: Charite, Humboldt Universität, Berlin, Germany

Authors and Affiliations

  1. Laboratories of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Caroline M. Groft, Andrej Sali & Stephen K. Burley

  2. Laboratories of Cell Biology, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Roland Beckmann

  3. Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Stephen K. Burley

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Correspondence to Stephen K. Burley.

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Groft, C., Beckmann, R., Sali, A. et al. Crystal structures of ribosome anti-association factor IF6. Nat Struct Mol Biol 7, 1156–1164 (2000). https://doi.org/10.1038/82017

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