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Protein Transport Across the Bacterial Plasma Membrane by the Sec Pathway

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Abstract

More than a third of all bacterial polypeptides, comprising the ‘exportome’, are transported to extracytoplasmic locations. Most of the exportome is targeted and inserts into (‘membranome’) or crosses (‘secretome’) the plasma membrane. The membranome and secretome use distinct targeting signals and factors, and driving forces, but both use the ubiquitous and essential Sec translocase and its SecYEG protein-conducting channel. Membranome export is co-translational and uses highly hydrophobic N-terminal signal anchor sequences recognized by the signal recognition particle on the ribosome, that also targets C-tail anchor sequences. Translating ribosomes drive movement of these polypeptides through the lateral gate of SecY into the inner membrane. On the other hand, secretome export is post-translational and carries two types of targeting signals: cleavable N-terminal signal peptides and multiple short hydrophobic targeting signals in their mature domains. Secretome proteins remain translocation competent due to occupying loosely folded to completely non-folded states during targeting. This is accomplished mainly by the intrinsic properties of mature domains and assisted by signal peptides and/or chaperones. Secretome proteins bind to the dimeric SecA subunit of the translocase. SecA converts from a dimeric preprotein receptor to a monomeric ATPase motor and drives vectorial crossing of chains through SecY aided by the proton motive force. Signal peptides are removed by signal peptidases and translocated chains fold or follow subsequent trafficking.

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Abbreviations

ATP/ADP:

Adenosine triphosphate/diphosphate

GTP:

Guanosine triphosphate

IM:

Inner membrane

IMP:

Inner membrane protein

IRA:

Intramolecular regulator of ATPase

MTS:

Mature targeting site

NBD:

Nucleotide binding domain

OM:

Outer membrane

PBD:

Preprotein binding domain

PG:

Phosphatidylglycerol

PMF:

Proton motive force

RBD:

Ribosome binding domain

RNC:

Ribosome nascent chain

SAS:

Signal anchor sequence

SBD:

Substrate binding domain

SD:

Scaffold domain

Sec pathway:

Secretory pathway

SP:

Signal peptide

SRP:

Signal recognition particle

STS:

Stop transfer sequence

TAMP:

Tail anchored membrane proteins

TAS:

Tail anchor sequence

TF:

Trigger factor

TM:

Transmembrane helix

References

  1. Castanie-Cornet MP et al (2014) Biochim Biophys Acta 1843(8):1442–1456

    Article  CAS  PubMed  Google Scholar 

  2. De Geyter J et al (2016) Nat Microbiol 1(8):16107

    Article  CAS  PubMed  Google Scholar 

  3. Bednarska NG et al (2013) Microbiology 159(Pt 9):1795–1806

    Article  CAS  PubMed  Google Scholar 

  4. Tsirigotaki A et al (2017) Nat Rev Microbiol 15(1):21–36

    Article  CAS  PubMed  Google Scholar 

  5. Blobel G et al (1975) J Cell Biol 67(3):835–851

    Article  CAS  PubMed  Google Scholar 

  6. Paetzel M (2014) Biochim Biophys Acta 1843(8):1497–1508

    Article  CAS  PubMed  Google Scholar 

  7. Orfanoudaki G et al (2014) Mol Cell Proteomics 13(12):3674–3687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Papanastasiou M et al (2013) Mol Cell Proteomics 12(3):599–610

    Article  CAS  PubMed  Google Scholar 

  9. Tsirigotaki T et al (2018) Structure 26(5):695–707 e5

    Article  CAS  PubMed  Google Scholar 

  10. Tam PC et al (2005) EMBO J 24(19):3380–3388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Van den Berg B et al (2004) Nature 427(6969):36–44

    Article  CAS  PubMed  Google Scholar 

  12. Kedrov A et al (2011) EMBO J 30(21):4387–4397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gold VA et al (2010) Proc Natl Acad Sci USA 107(22):10044–10049

    Article  PubMed  Google Scholar 

  14. Zimmer J et al (2008) Nature 455(7215):936–943

    Article  CAS  PubMed  Google Scholar 

  15. Manting EH et al (2000) Mol Microbiol 37(2):226–238

    Article  CAS  PubMed  Google Scholar 

  16. Dalbey RE et al (2014) Biochim Biophys Acta 1843(8):1489–1496

    Article  CAS  PubMed  Google Scholar 

  17. Schulze RJ et al (2014) Proc Natl Acad Sci USA 111(13):4844–4849

    Article  CAS  PubMed  Google Scholar 

  18. Tsukazaki T et al (2011) Nature 474(7350):235–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Saraogi I et al (2014) Biochim Biophys Acta 1843(8):1433–1441

    Article  CAS  PubMed  Google Scholar 

  20. Steinberg R (2018) FEMS Microbiol Lett 365:fny095

    Article  CAS  Google Scholar 

  21. Borgese N et al (2011) Biochim Biophys Acta 1808(3):937–946

    Article  CAS  PubMed  Google Scholar 

  22. Peschke M et al (2018) J Mol Biol 430(3):389–403

    Article  CAS  PubMed  Google Scholar 

  23. Hartl FU (2017) Annu Rev Biochem 86:21–26

    Article  CAS  PubMed  Google Scholar 

  24. Hoffmann A et al (2010) Biochim Biophys Acta 1803(6):650–661

    Article  CAS  PubMed  Google Scholar 

  25. Chatzi KE et al (2017) J Cell Biol 216(5):1357–1369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Huber D et al (2011) Mol Cell 41(3):343–353

    Article  CAS  PubMed  Google Scholar 

  27. Sala A et al (2014) Front Microbiol 5:666

    Article  PubMed  PubMed Central  Google Scholar 

  28. Prabudiansyah I et al (2017) Curr Top Microbiol Immunol 404:45–67

    PubMed  Google Scholar 

  29. van Wely KH et al (2001) FEMS Microbiol Rev 25(4):437–454

    Article  PubMed  Google Scholar 

  30. van Roosmalen ML et al (2004) Biochim Biophys Acta 1694(1–3):279–297

    Article  CAS  PubMed  Google Scholar 

  31. Bensing BA et al (2014) Biochim Biophys Acta 1843(8):1674–1686

    Article  CAS  PubMed  Google Scholar 

  32. Bensing BA et al (2002) Mol Microbiol 44(4):1081–1094

    Article  CAS  PubMed  Google Scholar 

  33. Braunstein M et al (2001) J Bacteriol 183(24):6979–6990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Seepersaud R et al (2010) Mol Microbiol 78(2):490–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bornemann T et al (2008) Nat Struct Mol Biol 15(5):494–499

    Article  CAS  PubMed  Google Scholar 

  36. Denks K et al (2017) Nat Microbiol 2:16265

    Article  CAS  PubMed  Google Scholar 

  37. Oh E et al (2011) Cell 147(6):1295–1308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kramer G et al (2018) Annu Rev Biochem. https://doi.org/10.1146/annurev-biochem-013118-111717

    Article  PubMed  Google Scholar 

  39. Kudva R et al (2018) Elife. https://doi.org/10.7554/eLife.36326

    Article  PubMed  PubMed Central  Google Scholar 

  40. von Heijne G (2006) Nat Rev Mol Cell Biol 7(12):909–918

    Article  CAS  Google Scholar 

  41. Kuhn A et al (2017) EcoSal Plus 174(5):715–724

    Google Scholar 

  42. Jomaa A et al (2016) Nat Commun 7:10471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Millman JS et al (2001) J Biol Chem 276(28):25982–25989

    Article  CAS  PubMed  Google Scholar 

  44. Janda CY et al (2010) Nature 465(7297):507–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Keenan RJ et al (1998) Cell 94(2):181–191

    Article  CAS  PubMed  Google Scholar 

  46. Freymann DM et al (1997) Nature 385(6614):361–364

    Article  CAS  PubMed  Google Scholar 

  47. Beckert B et al (2015) Nat Struct Mol Biol 22(10):767–773

    Article  CAS  PubMed  Google Scholar 

  48. Zhang X et al (2008) J Mol Biol 381(3):581–593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Peluso P et al (2001) Biochemistry 40(50):15224–15233

    Article  CAS  PubMed  Google Scholar 

  50. Focia PJ et al (2004) Science 303(5656):373–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Montoya G et al (1997) Nature 385(6614):365–368

    Article  CAS  PubMed  Google Scholar 

  52. Braig D et al (2011) Mol Biol Cell 22(13):2309–2323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Siu FY et al (2007) RNA 13(2):240–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Karniel A et al (2018) J Mol Biol 430(11):1607–1620

    Article  CAS  PubMed  Google Scholar 

  55. Prabudiansyah I et al (2015) Biochim Biophys Acta 1848(10 Pt A):2050–2056

    Article  CAS  PubMed  Google Scholar 

  56. Kuhn P et al (2015) J Cell Biol 211(1):91–104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Huber D et al (2017) J Bacteriol 199(2):e00622

    Article  CAS  PubMed  Google Scholar 

  58. Wang S et al (2017) J Cell Biol 216(11):3639–3653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Schibich D et al (2016) Nature 536(7615):219–223

    Article  CAS  PubMed  Google Scholar 

  60. Angelini S et al (2005) EMBO Rep 6(5):476–481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Draycheva A et al (2016) Mol Microbiol 102(1):152–167

    Article  CAS  PubMed  Google Scholar 

  62. von Loeffelholz O et al (2013) Nat Struct Mol Biol 20(5):604–610

    Article  CAS  Google Scholar 

  63. Akopian D et al (2013) J Cell Biol 200(4):397–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gasper R et al (2009) Nat Rev Mol Cell Biol 10(6):423–429

    Article  CAS  PubMed  Google Scholar 

  65. Halic M et al (2006) Science 312(5774):745–747

    Article  CAS  PubMed  Google Scholar 

  66. Frauenfeld J et al (2011) Nat Struct Mol Biol 18(5):614–621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gumbart J et al (2009) Structure 17(11):1453–1464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zhang X et al (2009) Proc Natl Acad Sci USA 106(6):1754–1759

    Article  PubMed  Google Scholar 

  69. Mitra K et al (2005) Nature 438(7066):318–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Deitermann S et al (2005) J Biol Chem 280(47):39077–39085

    Article  CAS  PubMed  Google Scholar 

  71. Koch HG et al (2002) J Biol Chem 277(8):5715–5718

    Article  CAS  PubMed  Google Scholar 

  72. Borgese N et al (2010) Traffic 11(7):877–885

    Article  CAS  PubMed  Google Scholar 

  73. Pross E et al (2016) J Mol Biol 428(20):4218–4227

    Article  CAS  PubMed  Google Scholar 

  74. Zalucki YM et al (2007) Biochem Biophys Res Commun 355(1):143–148

    Article  CAS  PubMed  Google Scholar 

  75. Zalucki YM et al (2011) Biochim Biophys Acta 1808(10):2544–2550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bibi E (2012) Trends Biochem Sci 37(1):1–6

    Article  CAS  PubMed  Google Scholar 

  77. Sardis MF et al (2017) Structure 25(7):1056–1067 e6

    Article  CAS  PubMed  Google Scholar 

  78. Singh P et al (2013) PLoS ONE 8(5):e63442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gouridis G et al (2013) Mol Cell 52(5):655–666

    Article  CAS  PubMed  Google Scholar 

  80. Vandenberk N et al (2018) Structure 27(1):90–101.06

    Article  CAS  PubMed  Google Scholar 

  81. Saio T et al (2018) Elife 7:e35731

    Article  PubMed  PubMed Central  Google Scholar 

  82. Guthrie B et al (1990) J Bacteriol 172(10):5555–5562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Schmidt A et al (2016) Nat Biotechnol 34(1):104–110

    Article  CAS  PubMed  Google Scholar 

  84. Merz F et al (2008) EMBO J 27(11):1622–1632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Saio T et al (2014) Science 344(6184):1250494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hoffmann A et al (2012) Mol Cell 48(1):63–74

    Article  CAS  PubMed  Google Scholar 

  87. Gelis I et al (2007) Cell 131(4):756–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Singh R et al (2014) J Biol Chem 289(10):7190–7199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bornemann T et al (2014) Nat Commun 5:4180

    Article  CAS  PubMed  Google Scholar 

  90. Jensen CG et al (1994) J Bacteriol 176(23):7148–7154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Huang C et al (2016) Nature 537(7619):202–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Xu Z et al (2000) Nat Struct Biol 7(12):1172–1177

    Article  CAS  PubMed  Google Scholar 

  93. Suo Y et al (2015) J Mol Biol 427(4):887–900

    Article  CAS  PubMed  Google Scholar 

  94. Schneewind O et al (2014) Biochim Biophys Acta 1843(8):1687–1697

    Article  CAS  PubMed  Google Scholar 

  95. Miller BK et al (2019) Elife 8:e40063

    Article  PubMed  PubMed Central  Google Scholar 

  96. Gouridis G et al (2009) Nature 462(7271):363–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hunt JF et al (2002) Science 297(5589):2018–2026

    Article  CAS  PubMed  Google Scholar 

  98. Erlandson KJ et al (2008) Nature 455(7215):984–987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bauer BW et al (2009) Proc Natl Acad Sci USA 106(49):20800–20805

    Article  PubMed  Google Scholar 

  100. Zimmer J et al (2009) J Mol Biol 394(4):606–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Collinson I (2017) J Bacteriol 199(2):e00736

    Article  CAS  PubMed  Google Scholar 

  102. Zimmer J et al (2006) J Mol Biol 364(3):259–265

    Article  CAS  PubMed  Google Scholar 

  103. Keramisanou D et al (2006) Nat Struct Mol Biol 13(7):594–602

    Article  CAS  PubMed  Google Scholar 

  104. Li L et al (2016) Nature 531(7594):395–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Rapoport TA et al (2017) Annu Rev Cell Dev Biol 33:369–390

    Article  CAS  PubMed  Google Scholar 

  106. Smith MA et al (2005) J Bacteriol 187(18):6454–6465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Benach J et al (2003) J Biol Chem 278(6):3628–3638

    Article  CAS  PubMed  Google Scholar 

  108. Dalal K et al (2012) Proc Natl Acad Sci USA 109(11):4104–4109

    Article  CAS  PubMed  Google Scholar 

  109. du Plessis DJ et al (2009) J Biol Chem 284(23):15805–15814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Corey RA et al (2016) Structure 24(4):518–527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Allen WJ et al (2016) Elife 5:e15598

    Article  PubMed  PubMed Central  Google Scholar 

  112. Bauer BW et al (2014) Cell 157(6):1416–1429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Braun V et al (2019) In: Kuhn A (ed) Bacterial cell walls and membranes, vol 92. Springer International Publishing

  114. Corey RA et al (2019) Elife 8:e41803

    Article  PubMed  PubMed Central  Google Scholar 

  115. Corey RA et al (2018) Proc Natl Acad Sci USA 115(31):7967–7972

    Article  CAS  PubMed  Google Scholar 

  116. Tsukazaki T (2018) FEMS Microbiol Lett 365(12):fny112

    Article  CAS  PubMed Central  Google Scholar 

  117. Thanassi DG et al (2005) Mol Membr Biol 22(1–2):63–72

    Article  CAS  PubMed  Google Scholar 

  118. Osborne AR et al (2004) Proc Natl Acad Sci USA 101(30):10937–10942

    Article  CAS  PubMed  Google Scholar 

  119. Dekker C et al (2003) J Struct Biol 144(3):313–319

    Article  CAS  PubMed  Google Scholar 

  120. Papanikolau Y et al (2007) J Mol Biol 366(5):1545–1557

    Article  CAS  PubMed  Google Scholar 

  121. Neidhardt FC et al (1996) Escherichia coli and Salmonella: cellular and molecular biology, 2nd edn. ASM Press, Washington, DC

    Google Scholar 

  122. Bakshi S et al (2012) Mol Microbiol 85(1):21–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Crooke E et al (1988) Cell 54(7):1003–1011

    Article  CAS  PubMed  Google Scholar 

  124. Findik BT et al (2017) PLoS ONE 12(8):e0183231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Woodbury RL et al (2000) J Biol Chem 275(31):24191–24198

    Article  CAS  PubMed  Google Scholar 

  126. Or E et al (2002) EMBO J 21(17):4470–4479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Deville K et al (2011) J Biol Chem 286(6):4659–4669

    Article  CAS  PubMed  Google Scholar 

  128. Urbanus ML et al (2002) J Biol Chem 277(15):12718–12723

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank G.Gouridis for help with structures.

Funding

Our research is funded through the: Research Foundation Flanders (FWO) [Grants #G.0B49.15 (to SK); #G0C6814N RiMembR and #G0C6814N CARBS (to AE)]; FWO/F.R.S.-FNRS “Excellence of Science-EOS” programme Grant #30550343 (to AE)]; EU (FP7 KBBE.2013.3.6-02: Synthetic Biology towards applications; #613877 StrepSynth; to AE); RUN (#RUN/16/001 KU Leuven; to AE) and C1 (ZKD4582—C16/18/008 KU Leuven; to SK and AE).

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Smets, D., Loos, M.S., Karamanou, S. et al. Protein Transport Across the Bacterial Plasma Membrane by the Sec Pathway. Protein J 38, 262–273 (2019). https://doi.org/10.1007/s10930-019-09841-8

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