A multipoint guidance mechanism for β-barrel folding on the SAM complex

Mitochondrial beta-barrel proteins are essential for the transport of metabolites, ions and proteins. The sorting and assembly machinery (SAM) mediates their folding and membrane insertion. We report the cryo-electron microscopy structure of the yeast SAM complex carrying an early eukaryotic beta-barrel folding intermediate. The lateral gate of Sam50 is wide open and pairs with the last beta-strand (beta-signal) of the substrate-the 19-beta-stranded Tom40 precursor-to form a hybrid barrel in the membrane plane. The Tom40 barrel grows and curves, guided by an extended bridge with Sam50. Tom40's first beta-segment (beta 1) penetrates into the nascent barrel, interacting with its inner wall. The Tom40 amino-terminal segment then displaces beta 1 to promote its pairing with Tom40's last beta-strand to complete barrel formation with the assistance of Sam37's dynamic alpha-protrusion. Our study thus reveals a multipoint guidance mechanism for mitochondrial beta-barrel folding.

Automated summary

Mitochondrial beta-barrel proteins play a vital role in transporting metabolites, ions, and proteins. The SAM complex is responsible for guiding their folding and inserting them into membranes. Our study presents the cryo-electron microscopy structure of the yeast SAM complex containing an early eukaryotic beta-barrel folding intermediate. The research reveals a multipoint guidance mechanism for mitochondrial beta-barrel folding, including the involvement of Sam50 and Sam37 in the process.