Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/96701
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Type: Journal article
Title: Identification of residues that underpin interactions within the eukaryotic initiation factor (eIF2) 2B complex
Author: Wang, X.
Wortham, N.
Liu, R.
Proud, C.
Citation: Journal of Biological Chemistry, 2012; 287(11):8263-8274
Publisher: American Society for Biochemistry and Molecular Biology
Issue Date: 2012
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Xuemin Wang, Noel C. Wortham, Rui Liu, and Christopher G. Proud
Abstract: Eukaryotic initiation factor 2B (eIF2B) plays a key role in protein synthesis and 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." eIF2Bγ and eIF2Bε contain homologous and conserved domains with sequence similarity to nucleotidyl transferases (NTs) and acyl transferases and can form a binary complex. The latter contain a hexad repeat that mainly comprises isoleucyl residues (hence termed the "I-patch" region). These 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 studied the functional effects of vanishing white matter 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: Nervous System Diseases
Rights: © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI: 10.1074/jbc.M111.331553
Appears in Collections:Aurora harvest 7
Molecular and Biomedical Science publications

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