Cryo-EM structure of the mitochondrial protein-import channel TOM complex from Saccharomyces cerevisiae.

Abstract

Nearly all mitochondrial proteins are encoded by the nuclear genome and imported into mitochondria following synthesis on cytosolic ribosomes. These precursor proteins are translocated into mitochondria by the TOM complex, a protein-conducting channel in the mitochondrial outer membrane. Using cryo-EM, we have obtained high-resolution structures of both apo and presequence-bound core TOM complexes from Saccharomyces cerevisiae in dimeric and tetrameric forms. Dimeric TOM consists of two copies each of five proteins arranged in two-fold symmetry--Tom40, a pore-forming {beta}-barrel with an overall negatively-charged inner surface, and four auxiliary -helical transmembrane proteins. The structure suggests that presequences for mitochondrial targeting insert into the Tom40 channel mainly by electrostatic and polar interactions. The tetrameric complex is essentially a dimer of dimeric TOM, which may be capable of forming higher-order oligomers. Our study reveals the molecular organization of the TOM complex and provides new insights about the mechanism of protein translocation into mitochondria.