scholarly journals Crystal structure of the MIF4G domain of the Trypanosoma cruzi translation initiation factor EIF4G5

2019 ◽  
Vol 75 (12) ◽  
pp. 738-743
Author(s):  
Lucca Pietro Camillo dos Santos ◽  
Bruno Moisés de Matos ◽  
Brenda Cecilia de Maman Ribeiro ◽  
Nilson Ivo Tonin Zanchin ◽  
Beatriz Gomes Guimarães
Keyword(s):  
Crystal Structure ◽  
Translation Initiation ◽  
Specific Interaction ◽  
Three Dimensional ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Dimensional Structure ◽  
Initiation Factors ◽  
Genes Encoding ◽  
Rna Complexes

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.

scholarly journals Functional interaction of translation initiation factor eIF4G with the foot-and-mouth disease virus internal ribosome entry site

2001 ◽  
Vol 82 (4) ◽  
pp. 757-763 ◽  
Author(s):  
Lanja Saleh ◽  
René C. Rust ◽  
Ralf Füllkrug ◽  
Ewald Beck ◽  
Gergis Bassili ◽  
...  
Keyword(s):  
Translation Initiation ◽  
Foot And Mouth Disease ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Entry Site ◽  
Stem Loop ◽  
Internal Ribosome Entry ◽  
Initiation Factors ◽  
Mouth Disease Virus ◽  
Ires Element

In the life-cycle of picornaviruses, the synthesis of the viral polyprotein is initiated cap-independently at the internal ribosome entry site (IRES) far downstream from the 5′ end of the viral plus-strand RNA. The cis-acting IRES RNA elements serve as binding sites for translation initiation factors that guide the ribosomes to an internal site of the viral RNA. In this study, we show that the eukaryotic translation initiation factor eIF4G interacts directly with the IRES of foot-and-mouth disease virus (FMDV). eIF4G binds mainly to the large Y-shaped stem–loop 4 RNA structure in the 3′ region of the FMDV IRES element, whereas stem–loop 5 contributes only slightly to eIF4G binding. Two subdomains of stem–loop 4 are absolutely essential for eIF4G binding, whereas another subdomain contributes to a lesser extent to binding of eIF4G. At the functional level, the translational activity of stem–loop 4 subdomain mutants correlates with the efficiency of binding of eIF4G in the UV cross-link assay. This indicates that the interaction of eIF4G with the IRES is crucial for the initiation of FMDV translation. A model for the interaction of initiation factors with the IRES element is discussed.

scholarly journals Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila

2005 ◽  
Vol 122 (4) ◽  
pp. 529-543 ◽  
Author(s):  
Greco Hernández ◽  
Michael Altmann ◽  
José Manuel Sierra ◽  
Henning Urlaub ◽  
Ruth Diez del Corral ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Genes Encoding

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

2009 ◽  
Vol 392 (4) ◽  
pp. 937-951 ◽  
Author(s):  
Takuya B. Hiyama ◽  
Takuhiro Ito ◽  
Hiroaki Imataka ◽  
Shigeyuki Yokoyama
Keyword(s):  
Crystal Structure ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Α Subunit

Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle

2000 ◽  
Vol 278 (1) ◽  
pp. E76-E82 ◽  
Author(s):  
O. Jameel Shah ◽  
Scot R. Kimball ◽  
Leonard S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Translation Initiation ◽  
Intraperitoneal Administration ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Nucleotide Exchange ◽  
Α Subunit ◽  
Initiation Factors

Glucocorticoids are diabetogenic factors that not only antagonize the action of insulin in target tissues but also render these tissues catabolic. Therefore, in rats, we endeavored to characterize the effects in skeletal muscle of glucocorticoids on translation initiation, a regulated process that, in part, governs overall protein synthesis through the modulated activities of eukaryotic initiation factors (eIFs). Four hours after intraperitoneal administration of dexamethasone (100 μg/100 g body wt), protein synthesis in skeletal muscle was reduced to 59% of the value recorded in untreated control animals. Furthermore, translation initiation factor eIF4E preferred association with its endogenous inhibitor 4E-BP1 rather than eIF4G. Dexamethasone treatment resulted in dephosphorylation of both 4E-BP1 and the 40S ribosomal protein S6 kinase concomitant with enhanced phosphorylation of eIF4E. Moreover, the guanine nucleotide exchange activity of eIF2B was unaffected as was phosphorylation of the α-subunit of eIF2. Hence glucocorticoids negatively modulate the activation of a subset of the protein synthetic machinery, thereby contributing to the catabolic properties of this class of hormones in vivo.

scholarly journals 2.4 Å resolution crystal structure of human TRAP1NM, the Hsp90 paralog in the mitochondrial matrix

2016 ◽  
Vol 72 (8) ◽  
pp. 904-911 ◽  
Author(s):  
Nuri Sung ◽  
Jungsoon Lee ◽  
Ji-Hyun Kim ◽  
Changsoo Chang ◽  
Francis T. F. Tsai ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Specific Interaction ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Dimensional Structure ◽  
Mitochondrial Matrix ◽  
Dimer Interface ◽  
Chaperone Function ◽  
Client Proteins ◽  
Mitochondrial Hsp70

TRAP1 is an organelle-specific Hsp90 paralog that is essential for neoplastic growth. As a member of the Hsp90 family, TRAP1 is presumed to be a general chaperone facilitating the late-stage folding of Hsp90 client proteins in the mitochondrial matrix. Interestingly, TRAP1 cannot replace cytosolic Hsp90 in protein folding, and none of the known Hsp90 co-chaperones are found in mitochondria. Thus, the three-dimensional structure of TRAP1 must feature regulatory elements that are essential to the ATPase activity and chaperone function of TRAP1. Here, the crystal structure of a human TRAP1NMdimer is presented, featuring an intact N-domain and M-domain structure, bound to adenosine 5′-β,γ-imidotriphosphate (ADPNP). The crystal structure together with epitope-mapping results shows that the TRAP1 M-domain loop 1 contacts the neighboring subunit and forms a previously unobserved third dimer interface that mediates the specific interaction with mitochondrial Hsp70.

Crystal structure of Arabidopsis translation initiation factor eIF-5A2

2009 ◽  
Vol 77 (3) ◽  
pp. 736-740 ◽  
Author(s):  
Yan-Bin Teng ◽  
Xiao-Xiao Ma ◽  
Yong-Xing He ◽  
Yong-Liang Jiang ◽  
Jin Du ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor
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