Keystone Symposia 2008 Conference Schedule Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on October 27, 2005, 10.1073/pnas.0507960102
PNAS | November 8, 2005 | vol. 102 | no. 45 | 16164-16169


This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supporting Information
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (10)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yamamoto, Y.
Right arrow Articles by Asano, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamamoto, Y.
Right arrow Articles by Asano, K.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

BIOCHEMISTRY
The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G

Yasufumi Yamamoto * {dagger}, Chingakham Ranjit Singh * {dagger}, Assen Marintchev {ddagger}, Nathan S. Hall *, Ernest M. Hannig §, Gerhard Wagner {ddagger}, and Katsura Asano *, ¶

*Molecular Cellular Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS 66506; {ddagger}Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; and §Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX 75083

Communicated by Charles C. Richardson, Harvard Medical School, Boston, MA, September 12, 2005 (received for review July 20, 2005)

Eukaryotic translation initiation factor (eIF) 5 is crucial for the assembly of the eukaryotic preinitiation complex. This activity is mediated by the ability of its C-terminal HEAT domain to interact with eIF1, eIF2, and eIF3 in the multifactor complex and with eIF4G in the 48S complex. However, the binding sites for these factors on eIF5–C-terminal domain (CTD) have not been known. Here we present a homology model for eIF5-CTD based on the HEAT domain of eIF2B{epsilon}. We show that the binding site for eIF2{beta} is located in a surface area containing aromatic and acidic residues (aromatic/acidic boxes), that the binding sites for eIF1 and eIF3c are located in a conserved surface region of basic residues, and that eIF4G binds eIF5-CTD at an interface overlapping with the acidic area. Mutations in these distinct eIF5 surface areas impair GCN4 translational control by disrupting preinitiation complex interactions. These results indicate that the eIF5 HEAT domain is a critical nucleation core for preinitiation complex assembly and function.

general amino acid control | ribosome preinitiation complex | translation initiation | translational control

Author contributions: G.W. and K.A. designed research; Y.Y., C.R.S., A.M., and N.S.H. performed research; A.M. analyzed data; E.M.H. contributed new reagents/analytic tools; and K.A. wrote the paper.

Conflict of interest statement: No conflicts declared.

Abbreviations: eIF, eukaryotic initiation factor; AA box, aromatic/acidic box; K box, lysine box; CTD, C-terminal domain; MFC, multifactor complex; TC, ternary complex; uORF, upstream ORF; Gcd, general control derepressed; Gcn, general control nonderepressible; FL, FLAG; HA, hemagglutinin; Ts–, temperature sensitive; 3AT, 3-aminotriazole.

{dagger} Y.Y. and C.R.S. contributed equally to this work.

To whom correspondence should be addressed. E-mail: kasano{at}ksu.edu.

© 2005 by The National Academy of Sciences of the USA


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 J. Biol. Chem.Home page
M. Reibarkh, Y. Yamamoto, C. R. Singh, F. del Rio, A. Fahmy, B. Lee, R. E. Luna, M. Ii, G. Wagner, and K. Asano
Eukaryotic Initiation Factor (eIF) 1 Carries Two Distinct eIF5-binding Faces Important for Multifactor Assembly and AUG Selection
J. Biol. Chem., January 11, 2008; 283(2): 1094 - 1103.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. S. Mohammad-Qureshi, R. Haddad, E. J. Hemingway, J. P. Richardson, and G. D. Pavitt
Critical Contacts between the Eukaryotic Initiation Factor 2B (eIF2B) Catalytic Domain and both eIF2{beta} and -2{gamma} Mediate Guanine Nucleotide Exchange
Mol. Cell. Biol., July 15, 2007; 27(14): 5225 - 5234.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
Y.-N. Cheung, D. Maag, S. F. Mitchell, C. A. Fekete, M. A. Algire, J. E. Takacs, N. Shirokikh, T. Pestova, J. R. Lorsch, and A. G. Hinnebusch
Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo
Genes & Dev., May 15, 2007; 21(10): 1217 - 1230.
[Abstract] [Full Text] [PDF]