Structural insight into the SAM-mediated assembly of the mitochondrial TOM core complex.

β-barrel outer membrane proteins (β-OMPs) play vital roles in mitochondria, chloroplasts, and Gram-negative bacteria. Evolutionarily conserved complexes such as the mitochondrial sorting and assembly machinery (SAM) mediate the assembly of β-OMPs. Here, we investigated the SAM-mediated assembly of the translocase of the outer membrane (TOM) core complex. Cryo-electron microscopy structures of SAM-fully folded Tom40 and the SAM-Tom40/Tom5/Tom6 complexes at ~3-A resolution reveal that Sam37 stabilizes the mature Tom40 mainly through electrostatic interactions, thus facilitating subsequent TOM assembly. These results support the β-barrel switching model and provide structural insights into the assembly and release of β-barrel complexes.