FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2035561674> ?p ?o ?g. }

• W2035561674 endingPage "1160" @default.
• W2035561674 startingPage "1159" @default.
• W2035561674 abstract "The outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria contain abundant β-barrel proteins that are essential for the transport of proteins and metabolites. Identification of the mitochondrial sorting and assembly machinery (SAM complex) revealed a new protein import pathway and sparked interest in mitochondrial β-barrel biogenesis. A central SAM component, Sam50, is conserved from bacteria to humans and a related protein is also found in chloroplasts, implying a conserved mechanism of β-barrel sorting in eukaryotes and prokaryotes (Pfanner et al., 2004Pfanner N. Wiedemann N. Meisinger C. Lithgow T. Nat. Struct. Mol. Biol. 2004; 11: 1044-1048Crossref PubMed Scopus (177) Google Scholar, Paschen et al., 2005Paschen S.A. Neupert W. Rapaport D. Trends Biochem. Sci. 2005; 30: 575-582Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, Dolezal et al., 2006Dolezal P. Likic V. Tachezy J. Lithgow T. Science. 2006; 313: 314-318Crossref PubMed Scopus (416) Google Scholar, Bos et al., 2007Bos M.P. Robert V. Tommassen J. Annu. Rev. Microbiol. 2007; 61: 191-214Crossref PubMed Scopus (334) Google Scholar). However, the other three SAM subunits have no homologs in bacteria or chloroplasts, and analysis of the bacterial β-signature sequence did not lead to the identification of a similar mitochondrial signal. In our Cell paper (Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar), we identified the sorting signal of mitochondrial β-barrel proteins in yeast and unexpectedly found that Sam35 functions as a receptor for the β-signal (Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar). In their Correspondence, Imai et al. report a detailed bioinformatics analysis of mitochondrial β-barrel proteins using the information derived from the β-signal. They propose a refinement of the β-signal by inclusion of a further hydrophobic residue in the motif. We experimentally demonstrated that four conserved residues of the β-signal are critical for its function, yielding the motif Po.G..Hy.Hy (Po, large polar residue; G, glycine; Hy, large hydrophobic residue) (Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar). The glycine residue is present in all known β-signals, whereas the other three residues are conserved in the vast majority of species. The amino acid following glycine is usually hydrophobic in most species, and so Imai et al. propose inclusion of this residue in a motif Po.GHy.Hy.Hy. However, at this position small hydrophobic residues like alanine are also found, and we experimentally demonstrated that replacement of the large hydrophobic residues in the C-terminal portion with alanine inhibits the function of the β-signal (Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar). Thus the motif Po.GHy.Hy.Hy proposed by Imai et al. (Hy, all hydrophobic residues) is inaccurate. It will be critical to discriminate between large and small hydrophobic residues, that is, the motif could be Po.Ghy.Hy.Hy (hy, hydrophobic residue; Hy, large hydrophobic residue). A detailed experimental analysis as performed for the other residues will be needed to validate this refined motif. Imai et al. note that the polar residue is not present in all β-signals as there is one example (Mdm10 in Schizosaccharomyces pombe) out of more than 50 β-signals with a hydrophobic residue at this position. This variation was already pointed out in our Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar paper. Given that the polar residue is highly conserved (>98% conserved in all known β-signals) and that we experimentally demonstrated its importance in Saccharomyces cerevisiae, we think this residue should remain in the β-motif. Imai et al. also propose that two more proteins, Mmm2 and Uth1, contain β-signals and should be included in our list of β-barrel proteins imported into mitochondria. These suggestions are valuable yet require experimental validation. So far we have not been able to obtain experimental evidence for the functional relevance of these putative β-signals and for import of Mmm2 or Uth1 via the SAM pathway. We agree with Imai et al. that the β-signal identified is present in all known mitochondrial β-barrel outer membrane proteins; however, we disagree with their suggestion that we may have reached the end of the analysis of eukaryotic β-barrel biogenesis. Their theoretical analysis likely will miss some β-barrel proteins. First, prediction programs that were trained on bacterial β-barrel proteins cannot reliably separate the β-barrel and non-β-barrel proteins of eukaryotes. Other programs for prediction of β-structures are mainly based on soluble β-proteins and thus are of limited value for transmembrane β-barrel proteins. Second, Imai et al. limited their analysis to proteins that were annotated as mitochondrial in databases. Given that databases not only include experimentally identified mitochondrial proteins but also proteins with a predicted mitochondrial location, they are biased toward proteins with N-terminal presequences (only those signals can be predicted by the available programs). Proteomic studies have indicated that numerous mitochondrial proteins, including β-barrel proteins, do not contain presequences, thus mitochondrial β-barrel proteins that have not yet been identified are simply excluded. Imai et al. correctly note that the proposal of more than 100 yeast mitochondrial β-barrel proteins (Wimley, 2003Wimley W.C. Curr. Opin. Struct. Biol. 2003; 13: 404-411Crossref PubMed Scopus (324) Google Scholar) is a clear overestimation. The mitochondrial outer membrane contains α-helical and β-barrel membrane proteins. Although β-barrel proteins like porin and Tom40 are highly abundant, the number of α-helical proteins likely exceeds that of β-barrel proteins. Given that recent proteomic studies indicated that the total number of resident yeast mitochondrial outer membrane proteins is below 100, it is evident that the number of β-barrel proteins is significantly lower. As the purified β-signal efficiently pulls down its receptor (Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar), purified SAM subunits may now be used in experiments to identify new substrate proteins. Third, Imai et al. briefly mention that mitochondrial β-barrel proteins lacking the β-signal would be missed in their analysis. Indeed, some bacterial β-barrel proteins do not contain the characteristic C-terminal signal (Bos et al., 2007Bos M.P. Robert V. Tommassen J. Annu. Rev. Microbiol. 2007; 61: 191-214Crossref PubMed Scopus (334) Google Scholar), raising interesting implications for the mitochondrial situation. Stojanovski et al., 2007Stojanovski D. Guiard B. Kozjak-Pavlovic V. Pfanner N. Meisinger C. J. Cell Biol. 2007; 179: 881-893Crossref PubMed Scopus (90) Google Scholar reported that an α-helical transmembrane protein, the receptor Tom22, uses the SAM machinery for insertion into the mitochondrial outer membrane. Tom22 does not contain the β-signal, and thus additional signals recognized by SAM likely exist. Fourth, Imai et al. do not address the second eukaryotic organelle of endosymbiotic origin, the chloroplast (Schleiff and Soll, 2005Schleiff E. Soll J. EMBO Rep. 2005; 6: 1023-1027Crossref PubMed Scopus (113) Google Scholar). The predicted β-barrel proteins of chloroplasts fall into two classes, the sorting signal being unknown in both. Thus, an experimental analysis of β-barrel proteins of chloroplasts will likely broaden our knowledge of the signals present in transmembrane β-barrel proteins. Regardless of their exact number, mitochondrial β-barrel proteins form a crucial class of proteins. Of all known outer membrane proteins, only three are essential for cell viability, the two β-barrel proteins Tom40 and Sam50 and the α-helical Sam35 that functions as a β-signal receptor (Kutik et al., 2008Kutik S. Stojanovski D. Becker L. Becker T. Meinecke M. Krüger V. Prinz C. Meisinger C. Guiard B. Wagner R. et al.Cell. 2008; 132: 1011-1024Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar). The linear analysis of Imai et al. misses an important message of our study, which is that the β-signal is a vital tool to characterize the mechanisms of a complex protein-sorting pathway. For example, the β-signal was used to identify the β-signal receptor and to study its integration into a hydrophilic transport channel and the subsequent insertion of the β-barrel precursors into the lipid phase of the mitochondrial outer membrane. We would like to emphasize that theoretical predictions are valuable for screening purposes and for generating hypotheses, but they cannot be used as the basis for claiming that a biological system is complete. The field of protein biogenesis has revealed numerous surprises. For example, although it was firmly believed that all transmembrane proteins of bacterial outer membranes are β-barrel proteins (also cited in Imai et al.), the elucidation of the structure of an α-helical outer membrane protein changed this view (Dong et al., 2006Dong C. Beis K. Nesper J. Brunkan-LaMontagne A.L. Clarke B.R. Whitfield C. Naismith J.H. Nature. 2006; 444: 226-229Crossref PubMed Scopus (252) Google Scholar). In the case of mitochondria, it was assumed that they possess only two major protein import pathways, yet subsequent studies identified two further import pathways that are essential for cell viability, including the β-barrel pathway (Dolezal et al., 2006Dolezal P. Likic V. Tachezy J. Lithgow T. Science. 2006; 313: 314-318Crossref PubMed Scopus (416) Google Scholar). Recently, the first structure of a mitochondrial β-barrel protein, human porin (VDAC-1) was solved (Hiller et al., 2008Hiller S. Garces R.G. Malia T.J. Orekhov V.Y. Colombini M. Wagner G. Science. 2008; 321: 1206-1210Crossref PubMed Scopus (505) Google Scholar). Surprisingly, the structure revealed a 19-stranded β-barrel, whereas all known bacterial β-barrel structures contain an even number of strands. It is tempting to speculate that barrel topology and insertion machinery coevolved in early mitochondria. Intracellular protein-sorting pathways show a remarkably high versatility, and the challenge will be to develop the concepts and experimental tools for elucidation of the molecular mechanisms of these pathways. Mitochondrial β-Barrel Proteins, an Exclusive Club?Imai et al.CellDecember 26, 2008In BriefMitochondria, chloroplasts, and Gram-negative bacteria have transporter proteins in their outer membranes called β-barrel proteins. The mechanism of integration of these proteins into the outer membrane of bacteria has been partly elucidated, including the identification of a C-terminal motif consisting of the terminal amino acid phenylalanine and additional hydrophobic residues close to the C terminus (Robert et al., 2006). However, little is known about the sequence characteristics that allow β-barrel proteins to integrate into the outer membrane of mitochondria. Full-Text PDF Open Archive" @default.
• W2035561674 created "2016-06-24" @default.
• W2035561674 creator A5014217628 @default.
• W2035561674 creator A5016283153 @default.
• W2035561674 creator A5016591234 @default.
• W2035561674 creator A5016767085 @default.
• W2035561674 creator A5020320687 @default.
• W2035561674 creator A5042624738 @default.
• W2035561674 creator A5044275464 @default.
• W2035561674 creator A5053307038 @default.
• W2035561674 creator A5061242251 @default.
• W2035561674 creator A5063691115 @default.
• W2035561674 creator A5065733862 @default.
• W2035561674 creator A5068752218 @default.
• W2035561674 creator A5081396858 @default.
• W2035561674 date "2008-12-01" @default.
• W2035561674 modified "2023-09-25" @default.
• W2035561674 title "Response: The Mitochondrial β-Signal and Protein Sorting" @default.
• W2035561674 cites W1986199954 @default.
• W2035561674 cites W2006349794 @default.
• W2035561674 cites W2028503280 @default.
• W2035561674 cites W2057566034 @default.
• W2035561674 cites W2075566732 @default.
• W2035561674 cites W2076583210 @default.
• W2035561674 cites W2078611261 @default.
• W2035561674 cites W2127177253 @default.
• W2035561674 cites W2164228620 @default.
• W2035561674 cites W2615823793 @default.
• W2035561674 doi "https://doi.org/10.1016/j.cell.2008.12.018" @default.
• W2035561674 hasPublicationYear "2008" @default.
• W2035561674 type Work @default.
• W2035561674 sameAs 2035561674 @default.
• W2035561674 citedByCount "2" @default.
• W2035561674 countsByYear W20355616742017 @default.
• W2035561674 crossrefType "journal-article" @default.
• W2035561674 hasAuthorship W2035561674A5014217628 @default.
• W2035561674 hasAuthorship W2035561674A5016283153 @default.
• W2035561674 hasAuthorship W2035561674A5016591234 @default.
• W2035561674 hasAuthorship W2035561674A5016767085 @default.
• W2035561674 hasAuthorship W2035561674A5020320687 @default.
• W2035561674 hasAuthorship W2035561674A5042624738 @default.
• W2035561674 hasAuthorship W2035561674A5044275464 @default.
• W2035561674 hasAuthorship W2035561674A5053307038 @default.
• W2035561674 hasAuthorship W2035561674A5061242251 @default.
• W2035561674 hasAuthorship W2035561674A5063691115 @default.
• W2035561674 hasAuthorship W2035561674A5065733862 @default.
• W2035561674 hasAuthorship W2035561674A5068752218 @default.
• W2035561674 hasAuthorship W2035561674A5081396858 @default.
• W2035561674 hasBestOaLocation W20355616741 @default.
• W2035561674 hasConcept C111696304 @default.
• W2035561674 hasConcept C199360897 @default.
• W2035561674 hasConcept C28859421 @default.
• W2035561674 hasConcept C41008148 @default.
• W2035561674 hasConcept C54355233 @default.
• W2035561674 hasConcept C86803240 @default.
• W2035561674 hasConcept C95444343 @default.
• W2035561674 hasConceptScore W2035561674C111696304 @default.
• W2035561674 hasConceptScore W2035561674C199360897 @default.
• W2035561674 hasConceptScore W2035561674C28859421 @default.
• W2035561674 hasConceptScore W2035561674C41008148 @default.
• W2035561674 hasConceptScore W2035561674C54355233 @default.
• W2035561674 hasConceptScore W2035561674C86803240 @default.
• W2035561674 hasConceptScore W2035561674C95444343 @default.
• W2035561674 hasIssue "7" @default.
• W2035561674 hasLocation W20355616741 @default.
• W2035561674 hasOpenAccess W2035561674 @default.
• W2035561674 hasPrimaryLocation W20355616741 @default.
• W2035561674 hasRelatedWork W1828691184 @default.
• W2035561674 hasRelatedWork W1920751942 @default.
• W2035561674 hasRelatedWork W1991523530 @default.
• W2035561674 hasRelatedWork W2002128513 @default.
• W2035561674 hasRelatedWork W2020824267 @default.
• W2035561674 hasRelatedWork W2031436818 @default.
• W2035561674 hasRelatedWork W2057739827 @default.
• W2035561674 hasRelatedWork W2075354549 @default.
• W2035561674 hasRelatedWork W2119103177 @default.
• W2035561674 hasRelatedWork W2092874662 @default.
• W2035561674 hasVolume "135" @default.
• W2035561674 isParatext "false" @default.
• W2035561674 isRetracted "false" @default.
• W2035561674 magId "2035561674" @default.
• W2035561674 workType "article" @default.