Structural insights into unique features of the human mitochondrial ribosome recycling

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 17; pp. 8283 - 8288
• Main Authors: Koripella, Ravi K., Sharma, Manjuli R., Risteff, Paul, Keshavan, Pooja, Agrawal, Rajendra K.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23.04.2019
• Subjects: Biological Sciences; Cryoelectron Microscopy; GTP Phosphohydrolases - chemistry; GTP Phosphohydrolases - metabolism; Guanosine triphosphatases; Humans; Mammals; Mitochondria; Mitochondrial Ribosomes - chemistry; Mitochondrial Ribosomes - metabolism; Mitochondrial Ribosomes - ultrastructure; Models, Molecular; Oxidative phosphorylation; Peptidyl Transferases - chemistry; Peptidyl Transferases - metabolism; Phosphorylation; Physical Sciences; Proteins; Recycling; Ribosomal Proteins - chemistry; Ribosomal Proteins - metabolism; Ribosomes; RNA, Ribosomal - chemistry; RNA, Ribosomal - metabolism; RNA, Transfer - chemistry; RNA, Transfer - metabolism; rRNA; tRNA; 55S–RRFmt complex; human mitochondrial RRF; mito-specific sequence; mito-specific interactions; cryo-EM structure
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1815675116

Mammalian mitochondrial ribosomes (mitoribosomes) are responsible for synthesizing proteins that are essential for oxidative phosphorylation (ATP generation). Despite their common ancestry with bacteria, the composition and structure of the human mitoribosome and its translational factors are significantly different from those of 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 3.9-Å resolution cryo-electron microscopic (cryo-EM) structure of the human 55S mitoribosome-RRFmt complex, which reveals α-helix and loop structures for the NTE that makes multiple mito-specific interactions with functionally critical regions of the mitoribosome. These include ribosomal RNA segments that constitute the peptidyl transferase center (PTC) and those that connect PTC with the GTPase-associated center and with mitoribosomal proteins L16 and L27. Our structure reveals the presence of a tRNA in the pe/E position and a rotation of the small mitoribosomal subunit on RRFmt binding. In addition, we observe an interaction between the pe/E tRNA and a mito-specific protein, mL64. These findings help understand the unique features of mitoribosome recycling.