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Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase

Translation initiation in eukaryotes relies on a complex network of interactions that are continuously reorganized throughout the process. As more information becomes available about the structure of the ribosomal preinitiation complex (PIC) at various points in translation initiation, new questions...

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Autores principales: Gamble, Nathan, Paul, Eleanor Elise, Anand, Bibin, Marintchev, Assen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508154/
https://www.ncbi.nlm.nih.gov/pubmed/36164648
http://dx.doi.org/10.1016/j.crstbi.2022.09.003
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author Gamble, Nathan
Paul, Eleanor Elise
Anand, Bibin
Marintchev, Assen
author_facet Gamble, Nathan
Paul, Eleanor Elise
Anand, Bibin
Marintchev, Assen
author_sort Gamble, Nathan
collection PubMed
description Translation initiation in eukaryotes relies on a complex network of interactions that are continuously reorganized throughout the process. As more information becomes available about the structure of the ribosomal preinitiation complex (PIC) at various points in translation initiation, new questions arise about which interactions occur when, their roles, and regulation. The eukaryotic translation factor (eIF) 5 is the GTPase-activating protein (GAP) for the GTPase eIF2, which brings the initiator Met-tRNA(i) to the PIC. eIF5 also plays a central role in PIC assembly and remodeling through interactions with other proteins, including eIFs 1, 1A, and 3c. Phosphorylation by casein kinase 2 (CK2) significantly increases the eIF5 affinity for eIF2. The interaction between eIF5 and eIF1A was reported to be mediated by the eIF5 C-terminal domain (CTD) and the eIF1A N-terminal tail. Here, we report a new contact interface, between eIF5-CTD and the oligonucleotide/oligosaccharide-binding fold (OB) domain of eIF1A, which contributes to the overall affinity between the two proteins. We also show that the interaction is modulated by dynamic intramolecular interactions within both eIF5 and eIF1A. CK2 phosphorylation of eIF5 increases its affinity for eIF1A, offering new insights into the mechanisms by which CK2 stimulates protein synthesis and cell proliferation.
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spelling pubmed-95081542022-09-25 Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase Gamble, Nathan Paul, Eleanor Elise Anand, Bibin Marintchev, Assen Curr Res Struct Biol Research Article Translation initiation in eukaryotes relies on a complex network of interactions that are continuously reorganized throughout the process. As more information becomes available about the structure of the ribosomal preinitiation complex (PIC) at various points in translation initiation, new questions arise about which interactions occur when, their roles, and regulation. The eukaryotic translation factor (eIF) 5 is the GTPase-activating protein (GAP) for the GTPase eIF2, which brings the initiator Met-tRNA(i) to the PIC. eIF5 also plays a central role in PIC assembly and remodeling through interactions with other proteins, including eIFs 1, 1A, and 3c. Phosphorylation by casein kinase 2 (CK2) significantly increases the eIF5 affinity for eIF2. The interaction between eIF5 and eIF1A was reported to be mediated by the eIF5 C-terminal domain (CTD) and the eIF1A N-terminal tail. Here, we report a new contact interface, between eIF5-CTD and the oligonucleotide/oligosaccharide-binding fold (OB) domain of eIF1A, which contributes to the overall affinity between the two proteins. We also show that the interaction is modulated by dynamic intramolecular interactions within both eIF5 and eIF1A. CK2 phosphorylation of eIF5 increases its affinity for eIF1A, offering new insights into the mechanisms by which CK2 stimulates protein synthesis and cell proliferation. Elsevier 2022-09-13 /pmc/articles/PMC9508154/ /pubmed/36164648 http://dx.doi.org/10.1016/j.crstbi.2022.09.003 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Gamble, Nathan
Paul, Eleanor Elise
Anand, Bibin
Marintchev, Assen
Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
title Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
title_full Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
title_fullStr Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
title_full_unstemmed Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
title_short Regulation of the interactions between human eIF5 and eIF1A by the CK2 kinase
title_sort regulation of the interactions between human eif5 and eif1a by the ck2 kinase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508154/
https://www.ncbi.nlm.nih.gov/pubmed/36164648
http://dx.doi.org/10.1016/j.crstbi.2022.09.003
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