Sandbox Reserved 327: Difference between revisions
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on one side with N-terminal tail (aa 1-23) or NTT <ref name="eIF1"/>. It is homolog to | on one side with N-terminal tail (aa 1-23) or NTT <ref name="eIF1"/>. It is homolog to | ||
<scene name='Sandbox_Reserved_327/Human_eif1/1'>human eIF1</scene> | <scene name='Sandbox_Reserved_327/Human_eif1/1'>human eIF1</scene> | ||
since it has 87% structure similarity and 63% identity (DNA sequence) to the human eIF1 <ref name="eIF1"/> <ref name="flet"/>. However, yeast eIF1 has two different conformations with two clear sets of backbone resonances that interconverting with each other and 20 different possible models for the N-terminal tail structure <ref name="eIF1"/>. So far, the binding sites of eIF1 to ribosome and eIF5 have been determined, while the exact | since it has 87% structure similarity and 63% identity (DNA sequence) to the human eIF1 <ref name="eIF1"/> <ref name="flet"/>. However, yeast eIF1 has two different conformations with two clear sets of backbone resonances that interconverting with each other and 20 different possible models for the N-terminal tail structure <ref name="eIF1"/>. So far, only the binding sites of eIF1 to ribosome and eIF5 have been determined, while the exact binding site interactions with other initiation proteins are still unknown <ref name="eIF1"/> <ref name="flet"/>. | ||
==eIF1-ribosome binding site== | ==eIF1-ribosome binding site== | ||
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''In vitro'' mutation in the eIF1-NTT area would alter the binding of eIF5 and eIF2β, but not eIF3c which supported that this area played role in stimulating the MFC assembly <ref name="eIF1"/>. ''In vivo'' study also supported that eIF1-NTT would allow the binding of eIF1 to the eIF5 and eIF2β <ref name="eIF1"/>. | ''In vitro'' mutation in the eIF1-NTT area would alter the binding of eIF5 and eIF2β, but not eIF3c which supported that this area played role in stimulating the MFC assembly <ref name="eIF1"/>. ''In vivo'' study also supported that eIF1-NTT would allow the binding of eIF1 to the eIF5 and eIF2β <ref name="eIF1"/>. | ||
===eIF1-KH=== | ===eIF1-KH=== | ||
The other binding site area of eIF1 to eIF5 which is believed to play role in the AUG start codon selection since ''in vitro'' mutation in this area by altering the basic | The other binding site area of eIF1 to eIF5 which is believed to play role in the AUG start codon selection since ''in vitro'' mutation in this area by altering the basic part of the KH region would relax the start codon selection <ref name="eIF1"/>.The mutation would also alter the formation of MFC, but not like mutation in the eIF1-NTT area, eIF1-NTT mutation is lethal to the yeast growth <ref name="eIF1"/>. Mutation that alter the hydrophobic residue would disrupt a critical link to the PIC and prevent the eIF1 dissociation <ref name="cheung"/>. The critical link is believed to be strongly associate with eIF5 <ref name="eIF1"/>. | ||
=Function and Mechanism= | =Function and Mechanism= | ||
[[Image:640px-Eukaryotic_initiation.png|thumb|left| | [[Image:640px-Eukaryotic_initiation.png|thumb|left|570px|Simplified model of eukaryotic initiation by [http://commons.wikimedia.org/wiki/User:Webridge Webridge]]] | ||
eIF1 is essential to control the ribosome conformational rearrangement in translation initiation by stimulating the formation of MFC and controlling the start codon selection which allow the translation elongation process to occur | eIF1 is essential to control the ribosome conformational rearrangement in translation initiation by stimulating the formation of MFC and controlling the start codon selection which allow the translation elongation process to occur | ||
<ref name="eIF1"/><ref name="asano"/>.Start codon selection is a key step for translation elongation to occur because recognition of the right AUG start codon would lead to the binding of 60S subunit to form the 80 S initiation complex, a precursor for elongation <ref name="eIF1"/>. Study showed eIF1 dissociation plays a critical role in start codon selection <ref name="cheung"/>. Initially, eIF1 in the 43S PIC would interact with the 5’end of mRNA to form 48S PIC and promotes scanning until the Met-tRNA<sub>i</sub><sup>Met</sup> recognizes the right AUG codon from the mRNA <ref name="eIF1"/><ref name="cheung"/>. Once the right codon is recognized, there would be a conformational change on the ribosome and the Met-tRNA<sub>i</sub><sup>Met</sup> would be released to the P-site, ready for the elongation process (paper, cheung). Also, hydrolysis of eIF2.GTP to GDP by the action of N-terminal residues of eIF5 in the PIC complex would occur, leading to a Pi being released <ref name="eIF1"/><ref name="cheung"/>. These two events would let the eIF1 and eIF2.GDP to be released from the PIC. Then, eIF5 GTPase would promote the binding of the ribosomal 60S forming the 80S ribosome, get it ready for elongation <ref name="eIF1"/>. The eIF2-GDP is then going to be re-used for another TC formation when it is recycled back to eIF2-GTP by eIF2B.GEF <ref name="eIF1"/>. However, when the codon-anticodon pair is mismatched, eIF1 would avoid the recognition by preventing the hydrolysis through blocking the Pi release at non-AUG codons and repressing the activity of eIF5 GTPase <ref name="eIF1"/><ref name="lomakin"/><ref name="cheung"/>. | <ref name="eIF1"/><ref name="asano"/>.Start codon selection is a key step for translation elongation to occur because recognition of the right AUG start codon would lead to the binding of 60S subunit to form the 80 S initiation complex, a precursor for elongation <ref name="eIF1"/>. Study showed eIF1 dissociation plays a critical role in start codon selection <ref name="cheung"/>. | ||
Initially, eIF1 in the 43S PIC would interact with the 5’end of mRNA to form 48S PIC and promotes scanning until the Met-tRNA<sub>i</sub><sup>Met</sup> recognizes the right AUG codon from the mRNA <ref name="eIF1"/><ref name="cheung"/>. Once the right codon is recognized, there would be a conformational change on the ribosome and the Met-tRNA<sub>i</sub><sup>Met</sup> would be released to the P-site, ready for the elongation process (paper, cheung). Also, hydrolysis of eIF2.GTP to GDP by the action of N-terminal residues of eIF5 in the PIC complex would occur, leading to a Pi being released <ref name="eIF1"/><ref name="cheung"/>. These two events would let the eIF1 and eIF2.GDP to be released from the PIC. Then, eIF5 GTPase would promote the binding of the ribosomal 60S forming the 80S ribosome, get it ready for elongation <ref name="eIF1"/>. The eIF2-GDP is then going to be re-used for another TC formation when it is recycled back to eIF2-GTP by eIF2B.GEF <ref name="eIF1"/>. However, when the codon-anticodon pair is mismatched, eIF1 would avoid the recognition by preventing the hydrolysis through blocking the Pi release at non-AUG codons and repressing the activity of eIF5 GTPase <ref name="eIF1"/><ref name="lomakin"/><ref name="cheung"/>. | |||
Mutations in eIF1 would alter the function and mechanism of eIF1 in the cell. There are two classesof mutations in yeast eIF1: ''Mof2'' and ''Sui1'' mutations <ref name="flet"/>. Mof2 mutation in eIF1 would increase the ribosome frameshifting in the translation process <ref name="flet"/>. As for ''Sui1'' mutation, | Mutations in eIF1 would alter the function and mechanism of eIF1 in the cell. There are two classesof mutations in yeast eIF1: ''Mof2'' and ''Sui1'' mutations <ref name="flet"/>. Mof2 mutation in eIF1 would increase the ribosome frameshifting in the translation process <ref name="flet"/>. As for ''Sui1'' mutation, | ||