HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 48, 49644-49655, November 26, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/48/49644    most recent M409609200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Singh, C. R. Articles by Asano, K. Search for Related Content PubMed PubMed Citation Articles by Singh, C. R. Articles by Asano, K. Social Bookmarking                      What's this?

Physical Association of Eukaryotic Initiation Factor (eIF) 5 Carboxyl-terminal Domain with the Lysine-rich eIF2 Segment Strongly Enhances Its Binding to eIF3^*

Chingakham Ranjit Singh, Yasufumi Yamamoto, and Katsura Asano

From the Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, Kansas 66506

The carboxyl-terminal domain (CTD) of eukaryotic initiation factor (eIF) 5 interacts with eIF1, eIF2, and eIF3c, thereby mediating formation of the multifactor complex (MFC), an important intermediate for the 43 S preinitiation complex assembly. Here we demonstrate in vitro formation of a nearly stoichiometric quaternary complex containing eIF1 and the minimal segments of eIF2, eIF3c, and eIF5. In vivo, overexpression of eIF2 and tRNA^Met_i suppresses the temperature-sensitive phenotype of tif5-7A altering eIF5-CTD by increasing interaction of the mutant eIF5 with eIF2 by mass action and restoring its defective interaction with eIF3. By contrast, overexpression of eIF1 exacerbated the tif5-7A phenotype because eIF1 forms unusual inhibitory complexes with a hyperstoichiometric amount of eIF1. Formation of such complexes leads to increased GCN4 translation, independent of eIF2 phosphorylation (general control derepressed or Gcd^– phenotype). We also provide biochemical evidence indicating that the association of eIF5-CTD with eIF2 strongly enhances its binding to eIF3c. Our results suggest strongly that MFC formation is an ordered event involving specific enhancement of eIF5-CTD binding to eIF3 on its binding to eIF2. We propose that the primary function of eIF5-CTD is to serve as an assembly guide by rapidly promoting stoichiometric MFC assembly with the aid of eIF2 while excluding formation of nonfunctional complexes.

Received for publication, August 20, 2004

^* This work was supported by the National Institutes of Health Centers of Biomedical Research Excellence Award 1 P20 RR15563, matching support from the State of Kansas and the Kansas State University, and National Institutes of Health Grant R01GM64781 (to K. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				P. V. Alone and T. E. Dever Direct Binding of Translation Initiation Factor eIF2{gamma}-G Domain to Its GTPase-activating and GDP-GTP Exchange Factors eIF5 and eIF2B{epsilon} J. Biol. Chem., May 5, 2006; 281(18): 12636 - 12644. [Abstract] [Full Text] [PDF]

				A. V. Jivotovskaya, L. Valasek, A. G. Hinnebusch, and K. H. Nielsen Eukaryotic Translation Initiation Factor 3 (eIF3) and eIF2 Can Promote mRNA Binding to 40S Subunits Independently of eIF4G in Yeast Mol. Cell. Biol., February 15, 2006; 26(4): 1355 - 1372. [Abstract] [Full Text] [PDF]

				Y. Yamamoto, C. R. Singh, A. Marintchev, N. S. Hall, E. M. Hannig, G. Wagner, and K. Asano The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G PNAS, November 8, 2005; 102(45): 16164 - 16169. [Abstract] [Full Text] [PDF]

				C. R. Singh, C. Curtis, Y. Yamamoto, N. S. Hall, D. S. Kruse, H. He, E. M. Hannig, and K. Asano Eukaryotic Translation Initiation Factor 5 Is Critical for Integrity of the Scanning Preinitiation Complex and Accurate Control of GCN4 Translation Mol. Cell. Biol., July 1, 2005; 25(13): 5480 - 5491. [Abstract] [Full Text] [PDF]