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

Figure 2.

Figure 2

β-Barrel switching mechanism for SAM-catalyzed assembly of the yeast TOM–CC. Recent cryo-EM structures (56) of the assembly intermediates support a β-barrel switch mechanism for SAM-mediated Tom40 folding. The SAM complex (comprised of Sam35-bound Sam50a and Sam37-bound Sam50b) serves as the chaperone complex for an incoming nascent β-barrel polypeptide. Interaction of the small Tim holdases carrying the nascent Tom40 precursor with the IMS face of Sam50a triggers the dissociation of Sam50b (step I), which initiates the folding of Tom40 in the membrane (step II), leading to formation of the SAM–Tom40 hybrid barrel (Intermediate I) (step III). Sam37 stabilizes the membrane-inserted Tom40 β-barrel by binding at its cytosolic face. The association of Tom5 and Tom6 to the hybrid barrel results in the formation of Intermediate II (step IV). Next, the binding of Tom7 and Tom22 (step V) triggers the dissociation of Tom40/5/6 and its release into the membrane (step Va). The subsequent dimerization of Tom40/5/6/7/22 gives rise to the TOM–CC (step VI). Mdm10 assists Tom40 release, by associating with Sam50a (step Vb). Binding of Sam50b to the hybrid Mdm10–Sam50a/35/37 complex allows reformation of the SAM complex, restoring the chaperone function of the SAM complex (8, 80). The cryo-EM structures (56) also reveal how Tom7 facilitates the dissociation of Tom40/5/6 from the SAM complex (see Fig. 3). Mdm, mitochondrial distribution and morphology; SAM, sorting and assembly machinery; TOM, translocase of the outer mitochondrial membrane; TOM–CC, TOM core complex; IMS, intermembrane space.