Article

Evolutionary conservation of biogenesis of β-barrel membrane proteins

Adolf-Butenandt-Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5, D-81377 München, Germany.
Nature (Impact Factor: 42.35). 01/2004; 426(6968):862-6. DOI: 10.1038/nature02208
Source: PubMed

ABSTRACT The outer membranes of mitochondria and chloroplasts are distinguished by the presence of beta-barrel membrane proteins. The outer membrane of Gram-negative bacteria also harbours beta-barrel proteins. In mitochondria these proteins fulfil a variety of functions such as transport of small molecules (porin/VDAC), translocation of proteins (Tom40) and regulation of mitochondrial morphology (Mdm10). These proteins are encoded by the nucleus, synthesized in the cytosol, targeted to mitochondria as chaperone-bound species, recognized by the translocase of the outer membrane, and then inserted into the outer membrane where they assemble into functional oligomers. Whereas some knowledge has been accumulated on the pathways of insertion of proteins that span cellular membranes with alpha-helical segments, very little is known about how beta-barrel proteins are integrated into lipid bilayers and assembled into oligomeric structures. Here we describe a protein complex that is essential for the topogenesis of mitochondrial outer membrane beta-barrel proteins (TOB). We present evidence that important elements of the topogenesis of beta-barrel membrane proteins have been conserved during the evolution of mitochondria from endosymbiotic bacterial ancestors.

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    • "The superfamily also includes transporters in membranes of various organelles of endosymbiotic origin. Thus, Sam50/Tob55 is the central piece of a complex that mediates protein insertion into the outer membrane of mitochondria, and it is likely that Toc75-V (Oep80) has a similar function in chloroplasts (Hsu and Inoue, 2009; Paschen et al., 2003; Patel et al., 2008; Schleiff and Soll, 2005). Toc75-III is the core of a hetero-oligomeric complex involved in translocating proteins from the cytosol across the outer membrane of chloroplasts (Schleiff et al., 2003; Sommer et al., 2011). "
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    • "To study whether MINOS was involved in outer membrane protein biogenesis, we used the radiolabeled precursor of Tom40 as a model substrate. For this precursor, three assembly stages can be resolved by blue native electrophoresis of digitonin-lysed mitochondria (Model et al., 2001; Paschen et al., 2003; Wiedemann et al., 2003; Ishikawa et al., 2004; Chan and Lithgow, 2008; Dukanovic et al., 2009). On incubation with isolated mitochondria, Tom40 forms intermediate I, which represents interaction of the precursor with the SAM complex (Model et al., 2001; Wiedemann et al., 2003; Becker et al., 2010). "
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    • "The assembly pathway of Tom40 involves several steps. On initial import of the precursor by the TOM complex to the intermembrane space side, intermembrane space chaperone complexes transfer Tom40 to the sorting and assembly machinery (SAM complex ) of the outer membrane (Model et al., 2001; Kozjak et al., 2003; Paschen et al., 2003; Wiedemann et al., 2003, 2004; Gentle et al., 2004; Hoppins and Nargang, 2004). The interaction of the Tom40 precursor with the SAM complex can be directly monitored by blue native electrophoresis after lysis of the mitochondria with the nonionic detergent digitonin (Ryan et al., 2001; Wittig et al., 2006; Stojanovski et al., 2007). "
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