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Structure paper

TitleMechanism of mitoribosomal small subunit biogenesis and preinitiation.
Journal, issue, pagesNature, Vol. 606, Issue 7914, Page 603-608, Year 2022
Publish dateJun 8, 2022
AuthorsYuzuru Itoh / Anas Khawaja / Ivan Laptev / Miriam Cipullo / Ilian Atanassov / Petr Sergiev / Joanna Rorbach / Alexey Amunts /
PubMed AbstractMitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) ...Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. ) outcompetes RBFA to complete the assembly with the SSU-mS37-mtIF3 complex that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.
External linksNature / PubMed:35676484 / PubMed Central
MethodsEM (single particle)
Resolution2.56 - 3.19 Å
Structure data

EMDB-13551, PDB-7pnt:
Assembly intermediate of mouse mitochondrial ribosome small subunit without mS37 in complex with RbfA and Tfb1m
Method: EM (single particle) / Resolution: 3.19 Å

EMDB-13552, PDB-7pnu:
Assembly intermediate of mouse mitochondrial ribosome small subunit without mS37 in complex with RbfA inward conformation
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-13553, PDB-7pnv:
Assembly intermediate of mouse mitochondrial ribosome small subunit without mS37 in complex with RbfA and Mettl15
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-13554, PDB-7pnw:
Mouse mitochondrial ribosome small subunit lacking m5U modification
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-13555, PDB-7pnx:
Assembly intermediate of human mitochondrial ribosome small subunit without mS37 in complex with RBFA and METTL15 conformation a
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-13556, PDB-7pny:
Assembly intermediate of human mitochondrial ribosome small subunit without mS37 in complex with RBFA and METTL15 conformation b
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-13557, PDB-7pnz:
Assembly intermediate of human mitochondrial ribosome small subunit without mS37 in complex with RBFA and METTL15 conformation c
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-13558, PDB-7po0:
Assembly intermediate of human mitochondrial ribosome small subunit without mS37 in complex with RBFA and IF3
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-13559, PDB-7po1:
Initiation complex of human mitochondrial ribosome small subunit with IF3
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-13560, PDB-7po2:
Initiation complex of human mitochondrial ribosome small subunit with IF2, fMet-tRNAMet and mRNA
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-13561, PDB-7po3:
Human mitochondrial ribosome small subunit
Method: EM (single particle) / Resolution: 2.92 Å

EMDB-13562, PDB-7po4:
Assembly intermediate of human mitochondrial ribosome large subunit (largely unfolded rRNA with MALSU1, L0R8F8 and ACP)
Method: EM (single particle) / Resolution: 2.56 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-HOH:
WATER / Water

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM / Nicotinamide adenine dinucleotide

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM / Guanosine diphosphate

ChemComp-FME:
N-FORMYLMETHIONINE / N-Formylmethionine

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-8Q1:
S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl] dodecanethioate

Source
  • mus musculus (house mouse)
  • homo sapiens (human)
KeywordsRIBOSOME / Assembly intermediate / maturation / biogenesis / small subunit / mitochondrion / Initiation factor 3 / translation

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