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

• DOI: 10.1038/s41594-022-00897-2
• Publication Date: 2023-01-05T17:04:38Z
• Authors: Hironori Takeda; Jon V. Busto; Caroline Lindau; Akihisa Tsutsumi; Kentaro Tomii; Kenichiro Imai; Yu Yamamori; Takatsugu Hirokawa; Chie Motono; Iniyan Ganesan; Lena-Sophie Wenz; Thomas Becker; Masahide Kikkawa; Nikolaus Pfanner; Nils Wiedemann; Toshiya Endo
• Keywords: Folding (DSP implementation)

Mitochondrial β-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 β-barrel folding intermediate. The lateral gate of Sam50 is wide open and pairs with the last β-strand (β-signal) of the substrate-the 19-β-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 β-segment (β1) penetrates into the nascent barrel, interacting with its inner wall. The Tom40 amino-terminal segment then displaces β1 to promote its pairing with Tom40's last β-strand to complete barrel formation with the assistance of Sam37's dynamic α-protrusion. Our study thus reveals a multipoint guidance mechanism for mitochondrial β-barrel folding.