Structural insights into unique features of the human mitochondrial ribosome recycling

Abstract

AbstractMammalian mitochondrial ribosomes (mitoribosomes) are responsible for synthesizing proteins that are essential for oxidative phosphorylation or energy (ATP) generation. Despite their proposed bacterial origin, the composition and structure of the human mitoribosome and its translational factors are dramatically different from their bacterial counterparts. The mammalian mitoribosome recycling factor (RRFmt) carries a mito-specific N-terminus extension (NTE), which is necessary for the function of RRFmt. Here we present a 3.7 Å resolution cryo-EM structure of the human 55S mitoribosome-RRFmt complex, which reveals α-helix and loop structures for a portion of the NTE that makes multiple mito-specific interactions with functionally critical regions of the mitoribosome. These include ribosomal RNAs segments that constitute the peptidyl transferase center (PTC), those that connect PTC with the GTPase-associated center, and with multiple mitoribosomal proteins. Our structure also reveals novel conformational changes in mitoribosome due to RRFmt binding. Together, these findings help understand the unique features of mitoribosome recycling.