Atomic structure of human TOM core complex

Wenhe Wang,Wei Zhuo,Maojun Yang,Jian Yin,Xudong Chen,Jinke Gu,Jingbo Yi,Laixing Zhang,Qingxi Ma

doi:10.1038/s41421-020-00198-2

Abstract

The translocase of the outer mitochondrial membrane (TOM) complex is the main entry gate for mitochondrial precursor proteins synthesized on cytosolic ribosomes. Here we report the single-particle cryo-electron microscopy (cryo-EM) structure of the dimeric human TOM core complex (TOM-CC). Two Tom40 β-barrel proteins, connected by two Tom22 receptor subunits and one phospholipid, form the protein-conducting channels. The small Tom proteins Tom5, Tom6, and Tom7 surround the channel and have notable configurations. The distinct electrostatic features of the complex, including the pronounced negative interior and the positive regions at the periphery and center of the dimer on the intermembrane space (IMS) side, provide insight into the preprotein translocation mechanism. Further, two dimeric TOM complexes may associate to form tetramer in the shape of a parallelogram, offering a potential explanation into the unusual structural features of Tom subunits and a new perspective of viewing the import of mitochondrial proteins.

Highlights

The translocase of the outer mitochondrial membrane (TOM) complex mediates the import of nuclear-encoded proteins into mitochondria
The PC molecule observed in the structure contributes to the tilted conformation of the Tom[40] pores and the structural integrity of the complex (Fig. 1f)
The positively charged choline group of PC extends into the intermembrane space (IMS) and enhances the regional positive charge contributed by the surfaces of Tom40s and Tom22s (Fig. 3a), suggesting that it could have a potential role in the activity of the TOM complex

Summary

Introduction

The translocase of the outer mitochondrial membrane (TOM) complex mediates the import of nuclear-encoded proteins into mitochondria. The human and fungal TOM-CC have notable structural and conformational differences in their respective subunits, indicating potentially divergent preprotein translocation mechanism, which would be discussed below in detail.

Results

Conclusion