ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery

Robin Corey, Zainab Ahdash, Anokhi Shah, Euan Pyle, William Allen, Tomas Fessl, Janet E Lovett, Argyris Politis, Ian Collinson

Research output: Contribution to journalArticle (Academic Journal)peer-review

19 Citations (Scopus)
224 Downloads (Pure)


Transport of proteins across membranes is a fundamental process, achieved in every cell by the 'Sec' translocon. In prokaryotes, SecYEG associates with the motor ATPase SecA to carry out translocation for pre-protein secretion. Previously, we proposed a Brownian ratchet model for transport, whereby the free energy of ATP-turnover favours the directional diffusion of the polypeptide [Allen et al. eLife 2016]. Here, we show that ATP enhances this process by modulating secondary structure formation within the translocating protein. A combination of molecular simulation with hydrogen-deuterium-exchange mass spectrometry and electron paramagnetic resonance spectroscopy reveal an asymmetry across the membrane: ATP induced conformational changes in the cytosolic cavity promote unfolded pre-protein structure, while the exterior cavity favours its formation. This ability to exploit structure within a pre-protein is an unexplored area of protein transport, which may apply to other protein transporters, such as those of the endoplasmic reticulum and mitochondria.
Original languageEnglish
Article numbere41803
Number of pages55
Early online date2 Jan 2019
Publication statusPublished - 2 Jan 2019

Bibliographical note

© 2019, Corey et al.


  • biochemistry
  • chemical biology
  • computational biology
  • E. coli
  • electron paramagnetic resonance (EPR) spectroscopy
  • hydrogen deuterium exchange (HDX) mass spectrometry
  • molecular dynamics
  • protein translocation
  • SecA
  • SecYEG
  • systems biology


Dive into the research topics of 'ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery'. Together they form a unique fingerprint.

Cite this