Reference: Takeda H, et al. (2023) A multipoint guidance mechanism for β-barrel folding on the SAM complex. Nat Struct Mol Biol 30(2):176-187

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Abstract


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.

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Journal Article | Research Support, Non-U.S. Gov't
Authors
Takeda H, Busto JV, Lindau C, Tsutsumi A, Tomii K, Imai K, Yamamori Y, Hirokawa T, Motono C, Ganesan I, ... Show all
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