Dataset Information

Mechanism of mitoribosomal small subunit biogenesis and preinitiation

ABSTRACT: Mitoribosomes are essential for synthesis and maintenance of bioenergetic proteins. Here, we use cryoelectron microscopy (cryo-EM) 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 METTL15 binding 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 outcompetes RBFA to complete the assembly with the SSU:mS37:mtIF3 complex that proceeds towards IF2 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Ilian Atanassov

LAB HEAD: Joanna Rorbach

PROVIDER: PXD031678 | Pride | 2022-07-11

REPOSITORIES: Pride

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			Action	DRS
	20210305_IA_JR_AK_HH_ML2_01_02.raw	Raw
	20210305_IA_JR_AK_HH_ML2_03_04.raw	Raw
	20210305_IA_JR_AK_HH_ML2_05.raw	Raw
	20210305_IA_JR_AK_HH_ML2_06.raw	Raw
	20210305_IA_JR_AK_HH_ML2_07.raw	Raw

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Mechanism of mitoribosomal small subunit biogenesis and preinitiation.

Itoh Yuzuru Y Khawaja Anas A Laptev Ivan I Cipullo Miriam M Atanassov Ilian I Sergiev Petr P Rorbach Joanna J Amunts Alexey A

Nature 20220608 7914

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 conformation ...[more]

PMID: 35676484

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