Crystal Structure of the C-terminal Domain of the Subunit of Human Translation Initiation Factor eIF2B
Eukaryotic translation initiation factor eIF2B, the guanine nucleotide exchange factor (GEF) for eIF2, catalyzes conversion of eIF2 {center_dot} GDP to eIF2 {center_dot} GTP. The eIF2B is composed of five subunits, {alpha}, {beta}, {gamma}, {delta} and {var_epsilon}, within which the {var_epsilon} subunit is responsible for catalyzing the guanine exchange reaction. Here we present the crystal structure of the C-terminal domain of human eIF2B{var_epsilon} (eIF2B{var_epsilon}-CTD) at 2.0-{angstrom} resolution. The structure resembles a HEAT motif and three charge-rich areas on its surface can be identified. When compared to yeast eIF2B{var_epsilon}-CTD, one area involves highly conserved AA boxes while the other two are only partially conserved. In addition, the previously reported mutations in human eIF2B{var_epsilon}-CTD, which are related to the loss of the GEF activity and human VWM disease, have been discussed. Based on the structure, most of such mutations tend to destabilize the HEAT motif.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1020245
- Report Number(s):
- BNL-96095-2011-JA; TRN: US201116%%225
- Journal Information:
- Protein and Cell, Vol. 1, Issue 6; ISSN 1674-800X
- Country of Publication:
- United States
- Language:
- English
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