EMD-31889
Tom20 subunits
EMD-31889
Single-particle13.0 Å
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Map released: 07/09/2022
Last modified: 04/09/2024
Sample Organism:
Homo sapiens
Sample: The translocase of the outer mitochondrial membrane of Tom20 subunit
Fitted models: 7vc9 (Avg. Q-score: 0.082)
Deposition Authors: Liu DS, Sui SF
Sample: The translocase of the outer mitochondrial membrane of Tom20 subunit
Fitted models: 7vc9 (Avg. Q-score: 0.082)
Deposition Authors: Liu DS, Sui SF
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Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.
Su J
,
Liu D,
Yang F,
Zuo MQ,
Li C,
Dong MQ
,
Sun S
,
Sui SF
(2022) PNAS , 119 , e2200158119 - e2200158119
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(2022) PNAS , 119 , e2200158119 - e2200158119
Abstract:
Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex components, Tom 20, Tom22, and Tom70, recognize the presequence and further guide the protein translocation. Their deficiency has been linked with neurodegenerative diseases and cardiac pathology. Although several structures of the TOM complex have been reported by cryoelectron microscopy (cryo-EM), how Tom22 and Tom20 function as TOM receptors remains elusive. Here we determined the structure of TOM core complex at 2.53 Å and captured the structure of the TOM complex containing Tom22 and Tom20 cytosolic domains at 3.74 Å. Structural analysis indicates that Tom20 and Tom22 share a similar three-helix bundle structural feature in the cytosolic domain. Further structure-guided biochemical analysis reveals that the Tom22 cytosolic domain is responsible for binding to the presequence, and the helix H1 is critical for this binding. Altogether, our results provide insights into the functional mechanism of the TOM complex recognizing and transferring preproteins across the mitochondrial membrane.
Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex components, Tom 20, Tom22, and Tom70, recognize the presequence and further guide the protein translocation. Their deficiency has been linked with neurodegenerative diseases and cardiac pathology. Although several structures of the TOM complex have been reported by cryoelectron microscopy (cryo-EM), how Tom22 and Tom20 function as TOM receptors remains elusive. Here we determined the structure of TOM core complex at 2.53 Å and captured the structure of the TOM complex containing Tom22 and Tom20 cytosolic domains at 3.74 Å. Structural analysis indicates that Tom20 and Tom22 share a similar three-helix bundle structural feature in the cytosolic domain. Further structure-guided biochemical analysis reveals that the Tom22 cytosolic domain is responsible for binding to the presequence, and the helix H1 is critical for this binding. Altogether, our results provide insights into the functional mechanism of the TOM complex recognizing and transferring preproteins across the mitochondrial membrane.