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. 2022 Mar 26;298(5):101870. doi: 10.1016/j.jbc.2022.101870

Figure 3.

Figure 3

Formation of TOM–CC from the SAM–Tom40 hybrid barrel. Tom40 of the SAM–Tom40 hybrid barrel (left; Intermediate I; PDB ID: 7E4H) associates directly with and binds Tom5 and Tom6 through electrostatic interactions, giving rise to Intermediate II (middle; SAM–Tom40/5/6; PDB ID: 7E4I). Tom5/6 binding additionally stabilizes Tom40, while Sam35 stabilizes the elliptical Sam50 barrel during this process (56). Cryo-EM structures of the Tom40–SAM complex reveal a common binding site for both Sam50 and Tom7 on the Tom40 β-barrel (right; purple oval; Tom7 coordinates from PDB ID: 6UCU superimposed on PDB ID: 7E4I), indicating that formation of Tom40–Sam50 and Tom40–Tom7 structures is mutually exclusive. Therefore, the association of Tom7 is anticipated to trigger the release of Tom40/5/6 from the SAM–Tom40 hybrid assembly. Tom7 therefore plays a vital role in the dissociation of Intermediate II (56). SAM, sorting and assembly machinery; TOM, translocase of the outer mitochondrial membrane; TOM–CC, TOM core complex.