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

Nature structural & molecular biology 2023 Feb

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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. © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Citation

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. A multipoint guidance mechanism for β-barrel folding on the SAM complex. Nature structural & molecular biology. 2023 Feb;30(2):176-187