EMD-13561
Human mitochondrial ribosome small subunit
EMD-13561
Single-particle2.92 Å
Deposition: 08/09/2021Map released: 15/06/2022
Last modified: 24/04/2024
Sample Organism:
Homo sapiens
Sample: Small subunit of human mitochondrial ribosome
Fitted models: 7po3 (Avg. Q-score: 0.593)
Deposition Authors: Itoh Y
,
Khawaja A
Sample: Small subunit of human mitochondrial ribosome
Fitted models: 7po3 (Avg. Q-score: 0.593)
Deposition Authors: Itoh Y
,
Khawaja A
Mechanism of mitoribosomal small subunit biogenesis and preinitiation.
Itoh Y ,
Khawaja A ,
Laptev I ,
Cipullo M,
Atanassov I ,
Sergiev P ,
Rorbach J ,
Amunts A
(2022) Nature , 606 , 603 - 608
,
Khawaja A ,
Laptev I ,
Cipullo M,
Atanassov I ,
Sergiev P ,
Rorbach J ,
Amunts A
(2022) Nature , 606 , 603 - 608
Abstract:
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. 1) outcompetes RBFA to complete the assembly with the SSU-mS37-mtIF3 complex2 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.
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. 1) outcompetes RBFA to complete the assembly with the SSU-mS37-mtIF3 complex2 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.