Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors

Su，Jiayue1; Liu，Desheng1; Yang，Fan1; Zuo，Mei Qing2; Li，Chang1; Dong，Meng Qiu2; Sun，Shan1; Sui，Sen Fang1,3

2022-06-28

10.1073/pnas.2200158119

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Impact Factor & Quartile

0027-8424

1091-6490

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.

cryo-EM mitochondria TOM complex Tom20 Tom22

SCI

English

NI Journal Papers

Corresponding

National Basic Research Program[2017YFA0504601] ; National Natural Science Foundation of China["32071192","91954118"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000854978700011

NATL ACAD SCIENCES

BIOLOGY & BIOCHEMISTRY;CLINICAL MEDICINE;MULTIDISCIPLINARY;PLANT & ANIMAL SCIENCE;ENVIRONMENT/ECOLOGY;SOCIAL SCIENCES, GENERAL;MICROBIOLOGY;ECONOMICS BUSINESS;IMMUNOLOGY;MATERIALS SCIENCE;MATHEMATICS;SPACE SCIENCE;MOLECULAR BIOLOGY & GENETICS;PHARMACOLOGY & TOXICOLOGY;CHEMISTRY;PSYCHIATRY/PSYCHOLOGY;NEUROSCIENCE & BEHAVIOR;PHYSICS;GEOSCIENCES;AGRICULTURAL SCIENCES;ENGINEERING

2-s2.0-85132626081

Scopus

1.State Key Laboratory of Membrane Biology,Beijing Advanced Innovation Center for Structural Biology,Beijing Frontier Research Center for Biological Structure,School of Life Sciences,Tsinghua University,100084,China
2.National Institute of Biological Sciences,102206,China
3.Department of Biology,Southern University of Science and Technology,Shenzhen,518055,China

Su，Jiayue,Liu，Desheng,Yang，Fan,et al. Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2022,119(26).

Su，Jiayue.,Liu，Desheng.,Yang，Fan.,Zuo，Mei Qing.,Li，Chang.,...&Sui，Sen Fang.(2022).Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,119(26).

Su，Jiayue,et al."Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119.26(2022).