Crystal structure of Arabidopsis
 translation initiation factor eIF-5A2

Kinetoplastida, a class of early-diverging eukaryotes that includes pathogenic Trypanosoma and Leishmania species, display key differences in their translation machinery compared with multicellular eukaryotes. One of these differences involves a larger number of genes encoding eIF4E and eIF4G homologs and the interaction pattern between the translation initiation factors. eIF4G is a scaffold protein which interacts with the mRNA cap-binding factor eIF4E, the poly(A)-binding protein, the RNA helicase eIF4A and the eIF3 complex. It contains the so-called middle domain of eIF4G (MIF4G), a multipurpose adaptor involved in different protein–protein and protein–RNA complexes. Here, the crystal structure of the MIF4G domain of T. cruzi EIF4G5 is described at 2.4 Å resolution, which is the first three-dimensional structure of a trypanosomatid MIF4G domain to be reported. Structural comparison with IF4G homologs from other eukaryotes and other MIF4G-containing proteins reveals differences that may account for the specific interaction mechanisms of MIF4G despite its highly conserved overall fold.

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Crystal Structure of the α Subunit of Human Translation Initiation Factor 2B

Journal of Molecular Biology ◽

10.1016/j.jmb.2009.07.054 ◽

2009 ◽

Vol 392 (4) ◽

pp. 937-951 ◽

Cited By ~ 22

Author(s):

Takuya B. Hiyama ◽

Takuhiro Ito ◽

Hiroaki Imataka ◽

Shigeyuki Yokoyama

Keyword(s):

Crystal Structure ◽

Translation Initiation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Α Subunit

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Faculty Opinions recommendation of Crystal structure of eukaryotic translation initiation factor 2B.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726166003.793522571 ◽

2016 ◽

Author(s):

Hyung Don Ryoo

Keyword(s):

Crystal Structure ◽

Translation Initiation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Eukaryotic Translation Initiation Factor ◽

Eukaryotic Translation ◽

Eukaryotic Translation Initiation

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Crystal structure of translation initiation factor IF2beta-IF2gamma complex

Acta Crystallographica Section A Foundations of Crystallography ◽

10.1107/s0108767305090331 ◽

2005 ◽

Vol 61 (a1) ◽

pp. c227-c227

Author(s):

M. Yao ◽

S. Toya ◽

N. Sakai ◽

M. Sokabe ◽

I. Tanaka

Keyword(s):

Crystal Structure ◽

Translation Initiation ◽

Translation Initiation Factor ◽

Initiation Factor

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Crystal Structure of the Archaeal Translation Initiation Factor 2 in Complex with a GTP Analogue and Met-tRNAfMet

Journal of Molecular Biology ◽

10.1016/j.jmb.2012.12.023 ◽

2013 ◽

Vol 425 (6) ◽

pp. 989-998 ◽

Cited By ~ 12

Author(s):

Elena Stolboushkina ◽

Stanislav Nikonov ◽

Natalia Zelinskaya ◽

Valentina Arkhipova ◽

Alexei Nikulin ◽

...

Keyword(s):

Crystal Structure ◽

Translation Initiation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Initiation Factor 2 ◽

Translation Initiation Factor 2

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Crystal structure of the ATPase domain of translation initiation factor 4A from Saccharomyces cerevisiae – the prototype of the DEAD box protein family

Structure ◽

10.1016/s0969-2126(99)80088-4 ◽

1999 ◽

Vol 7 (6) ◽

pp. 671-679 ◽

Cited By ~ 80

Author(s):

Jörg Benz ◽

Hans Trachsel ◽

Ulrich Baumann

Keyword(s):

Crystal Structure ◽

Saccharomyces Cerevisiae ◽

Translation Initiation ◽

Protein Family ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Atpase Domain ◽

Dead Box ◽

The Dead

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Crystal Structure of the RNA Recognition Motif of Yeast Translation Initiation Factor eIF3b Reveals Differences to Human eIF3b

PLoS ONE ◽

10.1371/journal.pone.0012784 ◽

2010 ◽

Vol 5 (9) ◽

pp. e12784 ◽

Cited By ~ 8

Author(s):

Sohail Khoshnevis ◽

Piotr Neumann ◽

Ralf Ficner

Keyword(s):

Crystal Structure ◽

Translation Initiation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Rna Recognition Motif ◽

Rna Recognition ◽

Recognition Motif

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A novel inhibitor stabilizes the inactive conformation of MAPK-interacting kinase 1

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x18002108 ◽

2018 ◽

Vol 74 (3) ◽

pp. 156-160 ◽

Cited By ~ 3

Author(s):

Yumi Matsui ◽

Isao Yasumatsu ◽

Ken-ichi Yoshida ◽

Shin Iimura ◽

Yutaka Ikeno ◽

...

Keyword(s):

Crystal Structure ◽

Translation Initiation ◽

Kinase Activity ◽

Translation Initiation Factor ◽

Mitogen Activated Protein Kinase ◽

Initiation Factor ◽

Structural Basis ◽

Eukaryotic Translation ◽

Mitogen Activated Protein ◽

Eukaryotic Translation Initiation

Mitogen-activated protein kinase (MAPK)-interacting kinases 1 (Mnk1) and 2 (Mnk2) modulate translation initiation through the phosphorylation of eukaryotic translation initiation factor 4E, which promotes tumorigenesis. However, Mnk1 and Mnk2 are dispensable in normal cells, suggesting that the inhibition of Mnk1 and Mnk2 could be effective in cancer therapy. To provide a structural basis for Mnk1 inhibition, a novel Mnk1 inhibitor was discovered and the crystal structure of Mnk1 in complex with this inhibitor was determined. The crystal structure revealed that the inhibitor binds to the autoinhibited state of Mnk1, stabilizing the Mnk-specific DFD motif in the DFD-out conformation, thus preventing Mnk1 from switching to the active conformation and thereby inhibiting the kinase activity. These results provide a valuable platform for the structure-guided design of Mnk1 inhibitors.

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