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TitleStructural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 119, Issue 26, Page e2200158119, Year 2022
Publish dateJun 28, 2022
AuthorsJiayue Su / Desheng Liu / Fan Yang / Mei-Qing Zuo / Chang Li / Meng-Qiu Dong / Shan Sun / Sen-Fang Sui /
PubMed AbstractMitochondrial 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 ...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.
External linksProc Natl Acad Sci U S A / PubMed:35733257 / PubMed Central
MethodsEM (single particle)
Resolution2.53 - 3.74 Å
Structure data

EMDB-31904, PDB-7vd2:
Human TOM complex without cross-linking
Method: EM (single particle) / Resolution: 2.53 Å

EMDB-31914, PDB-7vdd:
Human TOM complex with cross-linking
Method: EM (single particle) / Resolution: 3.74 Å

Chemicals

ChemComp-UND:
UNDECANE / Undecane

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

Source
  • homo sapiens (human)
KeywordsTRANSLOCASE / TOM core complex / Cryo-EM / Tom22 N-terminal domain

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