Structural insight into mitochondrial β-barrel outer membrane protein biogenesis

In mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 β-barrel opens a lateral gate to accommodate its substrates. The Sorting and Assembly Machinery (SAM) complex folds beta-barrel proteins and inserts them into the mitochondrial outer membrane. Here authors report cryoEM structures of the SAM complex from Myceliophthora thermophila, which reveals a GST-like fold for Sam35 and Sam37 and sheds light on how the Sam50 beta-barrel opens a lateral gate to accommodate its substrates.