Title:	High-Resolution Structural Analysis of Mitoribosomes in Complex with LRPPRC-SLIRP, MTIF2, and EF-Tu
DNr:	Berzelius-2025-58
Project Type:	LiU Berzelius
Principal Investigator:	Vlad-Julian Piljukov <vladjulian.piljukov@ki.se>
Affiliation:	Karolinska Institutet
Duration:	2025-02-18 – 2025-09-01
Classification:	10601
Homepage:	https://molmet.ki.se/rorbach
Keywords:

Abstract

Cryo-electron microscopy (cryo-EM) represents a transformative approach in structural biology, offering unparalleled resolution in the visualization of macromolecular complexes. This study aims to employ cryo-EM to investigate the structural dynamics of mitochondrial translation, with a particular focus on human mitoribosomes and their interactions with key translation factors, including LRPPRC-SLIRP, MTIF2, and EF-Tu. The primary objective of this research is to generate high-resolution three-dimensional reconstructions of mitoribosomal complexes at various stages of translation, thereby elucidating their conformational changes and functional mechanisms. Through cryo-EM analysis, we will delineate the structural basis of mitochondrial translation initiation, elongation, and termination, with an emphasis on the interplay between mitoribosomes, tRNAs, and translation factors. Furthermore, we will examine the structural implications of clinically relevant mutations in MTIF2, investigating their impact on mitochondrial translation initiation. This research will establish a comprehensive structural framework for understanding the regulatory mechanisms governing mitochondrial translation and their broader implications in human pathophysiology, including inherited metabolic disorders and neurodegenerative diseases. The cryo-EM datasets generated will be integral to deciphering the molecular determinants of translation factor recruitment, ribosomal structural rearrangements, and mRNA-tRNA interactions within mitochondria.