Identification of residues that underpin interactions within the eukaryotic initiation factor (eIF2) 2B complex
Wang, Xuemin, Wortham, Noel C., Liu, Rui and Proud, Christopher G. (2012) Identification of residues that underpin interactions within the eukaryotic initiation factor (eIF2) 2B complex. Journal of Biological Chemistry, 287, (11), 8263-8274. (doi:10.1074/jbc.M111.331553). (PMID:22238342).
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Eukaryotic initiation factor 2B (eIF2B) plays a key role in protein synthesis an in its control. It comprises five different subunits, α-ϵ, of which eIF2Bϵ contains the catalytic domain. Formation of the complete complex is crucial for full activity and proper control of eIF2B. Mutations in the genes for eIF2B cause an often-severe neurological disorder, vanishing white matter (VWM). eIF2Bγ and eIF2Bϵ contain homologous and conserved domains with sequence similarity to nucleotidyltransferases (ITs) and acyltransferases and can form a binary complex. The latter contain a hexad repeat that mainly comprises isoleucyl residues (hence termed the I-patch region). The present data reveal that certain residues in the NT domains of eIF2Bγ/ϵ, which are highly conserved throughout eukaryotes, play key roles in the interactions between subunits in the eIF2B complex. Our data show that the I-patch regions are important in the interactions between the catalytic eIF2Bγϵ complex and the other subunits. We also study the functional effects of VWM mutations in the NT and I-patch domains. Lastly, our data show that eIF2Bγ promotes the expression of eIF2Bϵ, providing a mechanism for achieving correct stoichiometry of these eIF2B subunits in the cell.
|Keywords:||protein domains, protein self-assembly, protein synthesis, translation, translation initiation factors, I-patch, eIF2B|
|Subjects:||Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Q Science > QP Physiology
|Divisions:||Faculty of Natural and Environmental Sciences > Biological Sciences > Molecular & Cellular
|Date Deposited:||20 Apr 2012 10:10|
|Last Modified:||28 Mar 2014 15:24|
Regulation and structural organisation of a key regulatory translation factor eIF2B
Funded by: BBSRC (BB/G008396/1)
Led by: Chris Proud
23 February 2009 to 22 August 2012
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