The EEF1 Family of Mammalian Translation Elongation Factors

Overview

Journal BBA Adv

Specialty Biochemistry

Date 2023 Apr 21

PMID 37082266

Authors

B S Negrutskii

V F Shalak

O V Novosylna

L V Porubleva

D M Lozhko

A V Elskaya

Affiliations

Soon will be listed here.

Abstract

The eEF1 family of mammalian translation elongation factors is comprised of the two variants of eEF1A (eEF1A1 and eEF1A2), and the eEF1B complex. The latter consists of eEF1Bα, eEF1Bβ, and eEF1Bγ subunits. The two eEF1A variants have similar translation activity but may differ with respect to their secondary, "moonlighting" functions. This variability is underlined by the difference in the spatial organization of eEF1A1 and eEF1A2, and also possibly by the differences in their post-translational modifications. Here, we review the data on the spatial organization and post-translation modifications of eEF1A1 and eEF1A2, and provide examples of their involvement in various processes in addition to translation. We also describe the structural models of eEF1B subunits, their organization in the subcomplexes, and the trimeric model of the entire eEF1B complex. We discuss the functional consequences of such an assembly into a complex as well as the involvement of individual subunits in non-translational processes.

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References

Dilworth D, Gudavicius G, Xu X, Boyce A, OSullivan C, Serpa J . The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability. Nucleic Acids Res. 2018; 46(5):2459-2478. PMC: 5861405. DOI: 10.1093/nar/gky008. View

Havrylenko S, Legouis R, Negrutskii B, Mirande M . Methionyl-tRNA synthetase from Caenorhabditis elegans: a specific multidomain organization for convergent functional evolution. Protein Sci. 2010; 19(12):2475-84. PMC: 3009414. DOI: 10.1002/pro.529. View

Peart J, Lu R, Sadanandom A, Malcuit I, Moffett P, Brice D . Ubiquitin ligase-associated protein SGT1 is required for host and nonhost disease resistance in plants. Proc Natl Acad Sci U S A. 2002; 99(16):10865-9. PMC: 125064. DOI: 10.1073/pnas.152330599. View

White K, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E . Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science. 2021; 371(6532):926-931. PMC: 7963220. DOI: 10.1126/science.abf4058. View

Engen J . Analysis of protein conformation and dynamics by hydrogen/deuterium exchange MS. Anal Chem. 2009; 81(19):7870-5. PMC: 2756691. DOI: 10.1021/ac901154s. View

Beckelman B, Day S, Zhou X, Donohue M, Gouras G, Klann E . Dysregulation of Elongation Factor 1A Expression is Correlated with Synaptic Plasticity Impairments in Alzheimer's Disease. J Alzheimers Dis. 2016; 54(2):669-78. PMC: 5439429. DOI: 10.3233/JAD-160036. View

Negrutskii B, Vlasenko D, Elskaya A . From global phosphoproteomics to individual proteins: the case of translation elongation factor eEF1A. Expert Rev Proteomics. 2012; 9(1):71-83. DOI: 10.1586/epr.11.71. View

Koo B, Chae S, Kim K, Kang M, Kim E, Kwak S . Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray. Diabetes. 2014; 63(9):3022-32. DOI: 10.2337/db13-1566. View

Jiang Y, Ning Y, Ma X, Liu Y, Wang Y, Zhang Z . Alteration of the proteome profile of the pancreas in diabetic rats induced by streptozotocin. Int J Mol Med. 2011; 28(2):153-60. DOI: 10.3892/ijmm.2011.696. View

10.

Anand N, Murthy S, Amann G, Wernick M, Porter L, Cukier I . Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nat Genet. 2002; 31(3):301-5. DOI: 10.1038/ng904. View

11.

Vanwetswinkel S, Kriek J, Andersen G, Guntert P, Dijk J, Canters G . Solution structure of the 162 residue C-terminal domain of human elongation factor 1Bgamma. J Biol Chem. 2003; 278(44):43443-51. DOI: 10.1074/jbc.M306031200. View

12.

Chalorak P, Dharmasaroja P, Meemon K . Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in Model. Front Neurosci. 2020; 14:303. PMC: 7212436. DOI: 10.3389/fnins.2020.00303. View

13.

Frau-Mendez M, Fernandez-Vega I, Ansoleaga B, Blanco Tech R, Tech M, Del Rio J . Fatal familial insomnia: mitochondrial and protein synthesis machinery decline in the mediodorsal thalamus. Brain Pathol. 2016; 27(1):95-106. PMC: 8029211. DOI: 10.1111/bpa.12408. View

14.

Perez J, Siegal G, Kriek J, Hard K, Dijk J, Canters G . The solution structure of the guanine nucleotide exchange domain of human elongation factor 1beta reveals a striking resemblance to that of EF-Ts from Escherichia coli. Structure. 1999; 7(2):217-26. DOI: 10.1016/s0969-2126(99)80027-6. View

15.

Jiang S, Wolfe C, Warrington J, Norcum M . Three-dimensional reconstruction of the valyl-tRNA synthetase/elongation factor-1H complex and localization of the delta subunit. FEBS Lett. 2005; 579(27):6049-54. DOI: 10.1016/j.febslet.2005.09.062. View

16.

Negrutskii B . Non-translational Connections of eEF1B in the Cytoplasm and Nucleus of Cancer Cells. Front Mol Biosci. 2020; 7:56. PMC: 7160314. DOI: 10.3389/fmolb.2020.00056. View

17.

Yaremchuk A, Shalak V, Novosylna O, Negrutskii B, Crepin T, Elskaya A . Purification, crystallization and preliminary X-ray crystallographic analysis of mammalian translation elongation factor eEF1A2. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012; 68(Pt 3):295-7. PMC: 3310534. DOI: 10.1107/S1744309112000243. View

18.

Janssen G, van Damme H, Kriek J, Amons R, Moller W . The subunit structure of elongation factor 1 from Artemia. Why two alpha-chains in this complex?. J Biol Chem. 1994; 269(50):31410-7. View

19.

Wu H, Wang C, Gong W, Wang J, Xuan J, Perrett S . The C-terminal region of human eukaryotic elongation factor 1Bδ. J Biomol NMR. 2016; 64(2):181-7. DOI: 10.1007/s10858-016-0012-6. View

20.

Hagiwara K, Katsuda T, Gailhouste L, Kosaka N, Ochiya T . Commitment of Annexin A2 in recruitment of microRNAs into extracellular vesicles. FEBS Lett. 2015; 589(24 Pt B):4071-8. DOI: 10.1016/j.febslet.2015.11.036. View