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Figure 5
A comparison of core TOM structures from lower and higher eukaryotes. (a) A superposition of the Drosophila and Neurospora structures, with key differences depicted in color: Neurospora crassa (PDB entry 8b4i) is in teal and Drosophila melanogaster (PDB entry 9etm) is in salmon pink. (b) The C-terminal helix (α3) and loop region of Neurospora Tom40, interacting with a minimal β3–β4 loop (teal), is viewed in the plane of the membrane. In Drosophila TOM, like other higher eukaryotes, the C-terminus is at the end of strand β19 and the proximal β3–β4 loop is more extended. The inset shows a close-up of the boxed area. (c) The C-terminal region of Neurospora Tom40 viewed from the inside of the Tom40 barrel, showing a Phe–Pro motif implicated in precursor binding. (d) The same view of Drosophila Tom40 shows that a similar motif is present but derives from the extended β3–β4 loop. Both folds are stabilized by hydrogen bonding. (e) An overlay of the β14–β15 loop of Tom40 in the two structures, showing the longer β-strands of the fungal TOMs. (f) Overlay showing Tom22 in color, showing ion-pairing interactions that influence the magnitude of the kink at a conserved proline. (g) Side-by-side views of Drosophila Tom7 and Neurospora Tom7, revealing the disposition of branched aliphatic side chains (Leu48, Leu51 and Leu52 in Drosophila; Leu45, Leu48 and Leu49 in Neurospora) on one face of the 310-helix. In Neurospora these favor intramolecular contacts with Tyr36 and Leu32 of Tom7, while in the Drosophila (and human) structures the side chains face away.

IUCrJ
Volume 12| Part 1| January 2025| Pages 49-61
ISSN: 2052-2525
https://doi.org/10.1107/S2052252524011011