Cryo-EM structure of the mitochondrial protein-import channel TOM complex at near-atomic resolution

Kyle Tucker; Eunyong Park

doi:10.1038/s41594-019-0339-2

Cryo-EM structure of the mitochondrial protein-import channel TOM complex at near-atomic resolution

Nat Struct Mol Biol. 2019 Dec;26(12):1158-1166. doi: 10.1038/s41594-019-0339-2. Epub 2019 Nov 18.

Authors

Kyle Tucker¹, Eunyong Park^{2

3}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
² Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. eunyong_park@berkeley.edu.
³ California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA. eunyong_park@berkeley.edu.

Abstract

Nearly all mitochondrial proteins are encoded by the nuclear genome and imported into mitochondria after synthesis on cytosolic ribosomes. These precursor proteins are translocated into mitochondria by the TOM complex, a protein-conducting channel in the mitochondrial outer membrane. We have determined high-resolution cryo-EM structures of the core TOM complex from Saccharomyces cerevisiae in dimeric and tetrameric forms. Dimeric TOM consists of two copies each of five proteins arranged in two-fold symmetry: pore-forming β-barrel protein Tom40 and four auxiliary α-helical transmembrane proteins. The pore of each Tom40 has an overall negatively charged inner surface attributed to multiple functionally important acidic patches. The tetrameric complex is essentially a dimer of dimeric TOM, which may be capable of forming higher-order oligomers. Our study reveals the detailed molecular organization of the TOM complex and provides new insights about the mechanism of protein translocation into mitochondria.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Carrier Proteins / chemistry*
Carrier Proteins / metabolism
Carrier Proteins / ultrastructure
Cryoelectron Microscopy
Mitochondria / metabolism
Mitochondrial Membrane Transport Proteins / chemistry*
Mitochondrial Membrane Transport Proteins / metabolism
Mitochondrial Membrane Transport Proteins / ultrastructure
Mitochondrial Precursor Protein Import Complex Proteins
Models, Molecular
Protein Conformation
Protein Multimerization
Protein Subunits / chemistry
Protein Subunits / metabolism
Protein Transport
Saccharomyces cerevisiae / chemistry*
Saccharomyces cerevisiae / metabolism
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / metabolism
Saccharomyces cerevisiae Proteins / ultrastructure

Substances

Carrier Proteins
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Protein Subunits
Saccharomyces cerevisiae Proteins
Tom40 protein, S cerevisiae

Grants and funding

T32 GM008295/GM/NIGMS NIH HHS/United States