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TitleVisualizing formation of the active site in the mitochondrial ribosome.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateOct 5, 2021
AuthorsViswanathan Chandrasekaran / Nirupa Desai / Nicholas O Burton / Hanting Yang / Jon Price / Eric A Miska / V Ramakrishnan /
PubMed AbstractRibosome assembly is an essential and conserved process that is regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of the conserved ...Ribosome assembly is an essential and conserved process that is regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of the conserved peptidyl transferase center (PTC) of the human mitochondrial ribosome. The conserved GTPase GTPBP7 regulates the correct folding of 16S ribosomal RNA (rRNA) helices and ensures 2'-O-methylation of the PTC base U3039. GTPBP7 binds the RNA methyltransferase NSUN4 and MTERF4, which sequester H68-71 of the 16S rRNA and allow biogenesis factors to access the maturing PTC. Mutations that disrupt binding of their orthologs to the large subunit potently activate mitochondrial stress and cause viability, development, and sterility defects. Next-generation RNA sequencing reveals widespread gene expression changes in these mutant animals that are indicative of mitochondrial stress response activation. We also answer the long-standing question of why NSUN4, but not its enzymatic activity, is indispensable for mitochondrial protein synthesis.
External linksElife / PubMed:34609277 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

13329

7pd3

EMDB-13329, PDB-7pd3:
Structure of the human mitoribosomal large subunit in complex with NSUN4.MTERF4.GTPBP7 and MALSU1.L0R8F8.mt-ACP
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-A:
ADENOSINE-5'-MONOPHOSPHATE

ChemComp-U:
URIDINE-5'-MONOPHOSPHATE

ChemComp-C:
CYTIDINE-5'-MONOPHOSPHATE

ChemComp-OMG:
O2'-METHYLGUANOSINE-5'-MONOPHOSPHATE

ChemComp-G:
GUANOSINE-5'-MONOPHOSPHATE

ChemComp-PSU:
PSEUDOURIDINE-5'-MONOPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-PNS:
4'-PHOSPHOPANTETHEINE

ChemComp-SAM:
S-ADENOSYLMETHIONINE

ChemComp-GCP:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-PCP, energy-carrying molecule analogue*YM

Source
  • homo sapiens (human)
  • Human (human)
KeywordsRIBOSOME / mitochondrial ribosome / large subunit / ribosome biogenesis / GTPase / rRNA modification

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