Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00537296" target="_blank" >RIV/61388971:_____/20:00537296 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/20:10422992

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2211124720315230" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124720315230</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2020.108534" target="_blank" >10.1016/j.celrep.2020.108534</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts

Popis výsledku v původním jazyce

Canonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires binding of initiator Met-tRNAiMet and several eukaryotic initiation factors (eIFs) to the small ribosomal subunit (40S). Compared to their mammalian hosts, trypanosomatids present significant structural differences in their 40S, suggesting substantial variability in translation initiation. Here, we determine the structure of the 43S PIC from Trypanosoma cruzi, the parasite causing Chagas disease. Our structure shows numerous specific features, such as the variant eIF3 structure and its unique interactions with the large rRNA expansion segments (ESs) 9S, 7S, and 6S, and the association of a kinetoplastid-specific DDX60-like helicase. It also reveals the 40S-binding site of the eIF5 C-terminal domain and structures of key terminal tails of several conserved eIFs underlying their activities within the PIC. Our results are corroborated by glutathione S-transferase (GST) pull-down assays in both human and T. cruzi and mass spectrometry data.

Název v anglickém jazyce

Structural Differences in Translation Initiation between Pathogenic Trypanosomatids and Their Mammalian Hosts

Popis výsledku anglicky

Canonical mRNA translation in eukaryotes begins with the formation of the 43S pre-initiation complex (PIC). Its assembly requires binding of initiator Met-tRNAiMet and several eukaryotic initiation factors (eIFs) to the small ribosomal subunit (40S). Compared to their mammalian hosts, trypanosomatids present significant structural differences in their 40S, suggesting substantial variability in translation initiation. Here, we determine the structure of the 43S PIC from Trypanosoma cruzi, the parasite causing Chagas disease. Our structure shows numerous specific features, such as the variant eIF3 structure and its unique interactions with the large rRNA expansion segments (ESs) 9S, 7S, and 6S, and the association of a kinetoplastid-specific DDX60-like helicase. It also reveals the 40S-binding site of the eIF5 C-terminal domain and structures of key terminal tails of several conserved eIFs underlying their activities within the PIC. Our results are corroborated by glutathione S-transferase (GST) pull-down assays in both human and T. cruzi and mass spectrometry data.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/GX19-25821X" target="_blank" >GX19-25821X: Regulace translace v nemoci na globální i transcript-specifické úrovni.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Reports

ISSN

2211-1247

e-ISSN

—

Svazek periodika

33

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

22

Strana od-do

108534

Kód UT WoS článku

000601399100012

EID výsledku v databázi Scopus

2-s2.0-85098072105