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. The Journal of Biological Chemistry, 287 (11), 8263-8274. (doi:10.1074/jbc.M111.331553). (PMID:22238342)

Abstract

Eukaryotic initiation factor 2B (eIF2B) plays a key role in protein synthesis an in its control. It comprises five different subunits, ?-?, of which eIF2B? 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). eIF2B? and eIF2B? 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 eIF2B?/?, 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 eIF2B?? 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 eIF2B? promotes the expression of eIF2B?, providing a mechanism for achieving correct stoichiometry of these eIF2B subunits in the cell.

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