Sandbox Reserved 324: Difference between revisions
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='''Human eIF2α (1q8k)'''= | |||
{{STRUCTURE_1q8k| PDB=1q8k | SCENE=Sandbox_Reserved_324/Default2/1}} | {{STRUCTURE_1q8k| PDB=1q8k | SCENE=Sandbox_Reserved_324/Default2/1}} | ||
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=Function= | =Function= | ||
The eIF2α subunit is considered to function primarily as a regulatory element of eIF2<ref name="1q8k"/>. The eIF2α is also the target of many kinases which become actived when the cell undergoes certain stresses<ref name="1q8k"/>. These kinases include PKR which is activated by virus infection, the heme regulated inhibitor(HRI) which is activated by iron deficiency, PERK which is activated by increased amounts of unfloded proteins in the ER, and GCN2 which is activated by amino acid starvation<ref name="1q8k"/>. As well, Ser51 has been identified as a phosphorylation site for these kinases<ref name="1q8k"/>. When phosporylation of Ser51 occurs it results in a strong inhibition of translation initiation<ref name="1q8k"/>. | |||
=References= | =References= | ||
<references/> | <references/> | ||
Revision as of 08:08, 4 April 2011
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
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Human eIF2α (1q8k)Human eIF2α (1q8k)
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| 1q8k, 15 NMR models () | |||||||||
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| Gene: | EIF2S1 OR EIF2A (Homo sapiens) | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
IntroductionIntroduction
The translation of proteins requires three steps to occur; initiation, elongation and termination. With each step one or more factors is involved in aiding the process. In eukaryotes initiation has the most factors that are essential for initiation to occur. eIF2 is one of the many initiating factors needed for eukaryotic initiation to occur. It is needed for proper initiation to occur. It initially binds to eIF2β in the presence of GTP. It then binds to Met-tRNAmeti and releases the eIF2β. This specific eIF2(1q8k) is the human eIF2α [1].
StructureStructure
The human eIF2 structure was determined by NMR spectroscopy[1]. The human eIF2 structure is a small structure made of two domains[1]. These two domains have a unique characteristic in that they are mobile relative to the other domain[1]. The N terminal domain (NTD) of the structure was discovered in previous years[2]. The N terminus is a β-barrel containing five anti-parallel β strands in an oligo-nucleotide binding domain(OB) fold [2]. The Ser-51 is where the phosphorylation/dephosphorylation occurs, which is found on the loop connecting β3 and β4 in the OB domain[2]. The second domain of the N terminus is a helical domain and it follows directly after the OB domain[2]. The first helix of this domain has large quantities of interactions, including a disulfide bridge, which allows adaptation of its orientation with respect to the OB domain[2]. The connection of the two domains is a likely site for protein-protein binding due to the highly conserved residues and negatively charged groove[2]. The C-terminal domain (CTD) for the human eIF2 was undetermined until the whole structure was discovered. The CTD contains a αβ-fold, which remarkably has a similar appearance to the CTD of eEF1Bα, a translation elongation factor, even though there is no sequence homology between the two[1]. eIF2α also has a topology of ββαββαβ, which is the same as eEF1Bα[1].
FunctionFunction
The eIF2α subunit is considered to function primarily as a regulatory element of eIF2[1]. The eIF2α is also the target of many kinases which become actived when the cell undergoes certain stresses[1]. These kinases include PKR which is activated by virus infection, the heme regulated inhibitor(HRI) which is activated by iron deficiency, PERK which is activated by increased amounts of unfloded proteins in the ER, and GCN2 which is activated by amino acid starvation[1]. As well, Ser51 has been identified as a phosphorylation site for these kinases[1]. When phosporylation of Ser51 occurs it results in a strong inhibition of translation initiation[1].
ReferencesReferences
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Ito T, Marintchev A, Wagner G. Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B. Structure. 2004 Sep;12(9):1693-704. PMID:15341733 doi:10.1016/j.str.2004.07.010
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Nonato MC, Widom J, Clardy J. Crystal structure of the N-terminal segment of human eukaryotic translation initiation factor 2alpha. J Biol Chem. 2002 May 10;277(19):17057-61. Epub 2002 Feb 21. PMID:11859078 doi:http://dx.doi.org/10.1074/jbc.M111804200