A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis

10.1038/ng717 ◽  
2001 ◽  
Vol 29 (1) ◽  
pp. 49-53 ◽  
Author(s):  
Sophie Mazeyrat ◽  
Noëmie Saut ◽  
Vladimir Grigoriev ◽  
Shantha K. Mahadevaiah ◽  
Obah A. Ojarikre ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Initiation Factor Eif2

scholarly journals Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michael Schoof ◽  
Lan Wang ◽  
J. Zachery Cogan ◽  
Rosalie E. Lawrence ◽  
Morgane Boone ◽  
...  
Keyword(s):  
Stress Response ◽  
Translation Initiation ◽  
Viral Proteins ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Nucleotide Exchange ◽  
Double Stranded Rna ◽  
Nucleotide Exchange Factor ◽  
Initiation Factor Eif2

AbstractViral infection triggers activation of the integrated stress response (ISR). In response to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates the translation initiation factor eIF2, converting it from a translation initiator into a potent translation inhibitor and this restricts the synthesis of viral proteins. Phosphorylated eIF2 (eIF2-P) inhibits translation by binding to eIF2’s dedicated, heterodecameric nucleotide exchange factor eIF2B and conformationally inactivating it. We show that the NSs protein of Sandfly Fever Sicilian virus (SFSV) allows the virus to evade the ISR. Mechanistically, NSs tightly binds to eIF2B (KD = 30 nM), blocks eIF2-P binding, and rescues eIF2B GEF activity. Cryo-EM structures demonstrate that SFSV NSs and eIF2-P directly compete, with the primary NSs contacts to eIF2Bα mediated by five ‘aromatic fingers’. NSs binding preserves eIF2B activity by maintaining eIF2B’s conformation in its active A-State.

scholarly journals The IE180 Protein of Pseudorabies Virus Suppresses Phosphorylation of Translation Initiation Factor eIF2 

2012 ◽  
Vol 86 (13) ◽  
pp. 7235-7240 ◽  
Author(s):  
N. Van Opdenbosch ◽  
C. Van den Broeke ◽  
N. De Regge ◽  
E. Tabares ◽  
H. W. Favoreel
Keyword(s):  
Translation Initiation ◽  
Pseudorabies Virus ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Initiation Factor Eif2 ◽  
Ie180 Protein

scholarly journals Viral Evasion of the Integrated Stress Response Through Antagonistic eIF2-P Mimicry

2021 ◽  
Author(s):  
Michael Schoof ◽  
Lan Wang ◽  
J Zachery Cogan ◽  
Rosalie Lawrence ◽  
Morgane Boone ◽  
...  
Keyword(s):  
Stress Response ◽  
Translation Initiation ◽  
Viral Proteins ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Nucleotide Exchange ◽  
Double Stranded Rna ◽  
Nucleotide Exchange Factor ◽  
Initiation Factor Eif2

Viral infection triggers activation of the integrated stress response (ISR). In response to viral double-stranded RNA (dsRNA), RNA-activated protein kinase (PKR) phosphorylates the translation initiation factor eIF2, converting it from a translation initiator into a potent translation inhibitor and this restricts the synthesis of viral proteins. Phosphorylated eIF2 (eIF2-P) inhibits translation by binding to eIF2's dedicated, heterodecameric nucleotide exchange factor eIF2B and conformationally inactivating it. We show that the NSs protein of Sandfly Fever Sicilian virus (SFSV) allows the virus to evade the ISR. Mechanistically, NSs tightly binds to eIF2B (KD = 43 nM), blocks eIF2-P binding, and rescues eIF2B GEF activity. Cryo-EM structures demonstrate that SFSV NSs and eIF2-P directly compete, with the primary NSs contacts to eIF2Bα; mediated by five 'aromatic fingers'. NSs binding preserves eIF2B activity by maintaining eIF2B's conformation in its active A-State.;

scholarly journals Mutations in the NKXD consensus element indicate that GTP binds to the γ-subunit of translation initiation factor eIF2

FEBS Letters ◽  
1995 ◽  
Vol 372 (2-3) ◽  
pp. 249-252 ◽  
Author(s):  
Tatjana Naranda ◽  
Ivana Sirangelo ◽  
Bradon J. Fabbri ◽  
John W.B. Hershey
Keyword(s):  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Γ Subunit ◽  
Initiation Factor Eif2

scholarly journals Structural basis for the inhibition of translation through eIF2α phosphorylation

2018 ◽  
Author(s):  
Yuliya Gordiyenko ◽  
José Luis Llácer ◽  
Venki Ramakrishnan
Keyword(s):  
Translation Initiation ◽  
Ternary Complex ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Cells ◽  
Structural Basis ◽  
Eif2α Phosphorylation ◽  
Α Subunits ◽  
Initiation Factor Eif2 ◽  
Phosphate Groups

AbstractOne of the responses to stress by eukaryotic cells is the down-regulation of protein synthesis by phosphorylation of translation initiation factor eIF2. Phosphorylation results in low availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting its interaction with its GTP-GDP exchange factor eIF2B. We have determined the cryo-EM structure of eIF2B in complex with phosphorylated eIF2 at an overall resolution of 4.15 Å. Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2α-D1, which contains the phosphorylated Ser51. eIF2α-D1 is mainly inserted between the N-terminal helix bundle domains of δ and α subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Bα and indirectly by inducing contacts of eIF2α helix 58-63 with eIF2Bδ leading to a competition with Met-tRNAi.

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