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

Abstract

9Nearly all mitochondrial proteins are encoded by the nuclear genome and imported into mitochondria 10 following synthesis on cytosolic ribosomes. These precursor proteins are translocated into mitochondria 11 by the TOM complex, a protein-conducting channel in the mitochondrial outer membrane. Using cryo-EM, 12we have obtained high-resolution structures of both apo and presequence-bound core TOM complexes 13from Saccharomyces cerevisiae in dimeric and tetrameric forms. Dimeric TOM consists of two copies each of 14 five proteins arranged in two-fold symmetry-Tom40, a pore-forming β-barrel with an overall negatively-15 charged inner surface, and four auxiliary α-helical transmembrane proteins. The structure suggests that 16 presequences for mitochondrial targeting insert into the Tom40 channel mainly by electrostatic and polar 17interactions. The tetrameric complex is essentially a dimer of dimeric TOM, which may be capable of 18forming higher-order oligomers. Our study reveals the molecular organization of the TOM complex and 19provides new insights about the mechanism of protein translocation into mitochondria. 20 21