EMD-10021
Structure of human mitochondrial 28S ribosome in complex with mitochondrial IF3
EMD-10021
Single-particle2.97 Å
Deposition: 03/06/2019
Map released: 03/06/2020
Last modified: 24/04/2024
Sample Organism:
Homo sapiens
Sample: IF3 bound mitochondrial translation pre-initiation complex
Fitted models: 6rw4 (Avg. Q-score: 0.599)
Deposition Authors: Itoh Y , Khawaja A
Sample: IF3 bound mitochondrial translation pre-initiation complex
Fitted models: 6rw4 (Avg. Q-score: 0.599)
Deposition Authors: Itoh Y , Khawaja A
Distinct pre-initiation steps in human mitochondrial translation.
Khawaja A ,
Itoh Y ,
Remes C ,
Spahr H,
Yukhnovets O,
Hofig H ,
Amunts A ,
Rorbach J
(2020) Nat Commun , 11 , 2932 - 2932
(2020) Nat Commun , 11 , 2932 - 2932
Abstract:
Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammalian protein synthesis that are specific to mitochondria.
Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammalian protein synthesis that are specific to mitochondria.