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
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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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DOI: https://doi.org/10.1007/s10930-019-09841-8