TY - JOUR TI - ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery AU - Corey, Robin A AU - Ahdash, Zainab AU - Shah, Anokhi AU - Pyle, Euan AU - Allen, William J AU - Fessl, Tomas AU - Lovett, Janet E AU - Politis, Argyris AU - Collinson, Ian A2 - Shan, Yibing A2 - Kuriyan, John VL - 8 PY - 2019 DA - 2019/01/02 SP - e41803 C1 - eLife 2019;8:e41803 DO - 10.7554/eLife.41803 UR - https://doi.org/10.7554/eLife.41803 AB - 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., 2016). Here, we show that ATP enhances this process by modulating secondary structure formation within the translocating protein. A combination of molecular simulation with hydrogendeuterium-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. KW - SecA KW - SecYEG KW - protein translocation KW - molecular dynamics KW - hydrogen deuterium exchange (HDX) mass spectrometry KW - electron paramagnetic resonance (EPR) spectroscopy JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -