Fadel Fakih

@fakih98.bsky.social

Third year PhD student at Julius Lukes Lab @BiologyCentre Studying tRNAs and translation in protists.

Structural basis for emetine inhibition of ribosome translocation in Toxoplasma gondii bioRxivpreprint

Structural basis for emetine inhibition of ribosome translocation in Toxoplasma gondii

Apicomplexan parasites, including Toxoplasma gondii and Plasmodium falciparum, are major human pathogens that cause toxoplasmosis and malaria, respectively. The existing structures of T. gondii translational machinery are from empty ribosomes that lack several key components, including ribosomal protein RACK1 (Receptor for Activated C Kinase 1). Here, we used cryo-electron microscopy (cryoEM) to determine high-resolution structures of T. gondii ribosomal complexes, including a translating 80S ribosome bound to mRNA and tRNA. These structures reveal that RACK1 occupies the conserved binding site on the 40S subunit observed in other eukaryotic ribosomes. We also determined the architecture of the ribosomal P-stalk and identified the ribosomal proteins uL10 and uL11, which were not observed in previous T. gondii ribosome structures. In addition, we determined structures of the 80S ribosome bound to mRNA, tRNA, and the translation inhibitor emetine in two distinct conformational states. These snapshots reveal two mechanisms by which emetine inhibits the translocation step of mRNA translation: either by dislodging the mRNA from the E-site of the ribosome or by acting as a molecular glue within the E-site, thereby stalling translocation. Together, these findings provide new insights into the molecular basis of protein synthesis in apicomplexan parasites and establish a structural framework for the development of future antiparasitic therapeutics.

dlvr.it

Trypanosomal MICOS is assembled on non-respiring mitochondrial crista precursors and associates with two integral microproteins bioRxivpreprint

Trypanosomal MICOS is assembled on non-respiring mitochondrial crista precursors and associates with two integral microproteins

The mitochondrial contact site and cristae organizing system (MICOS) is a multiprotein complex that shapes crista junctions and maintains inner and outer membrane contacts. MICOS coordinates the assembly of electron transport chain complexes, a prerequisite for cellular respiration. Indeed, MICOS is lost in eukaryotes that dispensed with cellular respiration, suggesting that its assembly depends on the presence of an active respiratory chain. Trypanosoma brucei provides a unique system to test this hypothesis as its mitochondrion undergoes developmentally regulated remodeling. In the insect stage, the mitochondrion contains cristae with an active electron transport chain, whereas the mammalian bloodstream form possesses precursor cristae with stub-like morphology that lack respiratory activity. MICOS has been characterized in the insect stage but remains unexamined in the bloodstream form. Here, we demonstrate that all MICOS subunits assemble onto precursor cristae, retaining conserved interactions with both outer and inner membrane protein machineries. This is somewhat unexpected given the co-occurrence of MICOS with active cellular respiration in nature. Furthermore, we identify novel MICOS-associated proteins that are dispensable for its stability, suggesting auxiliary rather than core roles in MICOS function. Together, our findings establish that MICOS assembly precedes cellular respiratory competence and expand its interaction landscape in trypanosomatids.

dlvr.it

Whether condensates have real biological functions has long been debated. Our new Molecular Cell Perspective argues translation is a core one, not just repression. Next: live high-res imaging + probing condensate dynamics should let us get at where translation starts and how condensates shape it.

https://www.sciencedirect.com/science/article/pii/S1097276526003758

Do experiments in model organisms reveal universal biological rules, or only local regularities shaped by evolutionary history? Here is a short synthesis, inspired by our work, on how comparative genomics helps us distinguish between the two. #PhD #Biology #RNA rnastuff.com/2026/05/10/c...

Comparative Genomics, and the Boundaries of Molecular Rules

The evolution of life on Earth is a history of countless successes and failures. The variations arise through chance, but within physical, chemical, and biological organization and limitations. Nat…

rnastuff.com