期刊
ELIFE
卷 11, 期 -, 页码 -出版社
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.77586
关键词
protein secretion; membrane transport; SecYEG; SecA; protein translocation; E; coli
类别
资金
- Wellcome Trust [104632]
- Biotechnology and Biological Sciences Research Council [BB/S008349/1, BB/N015126/1, BB/M003604/1, BB/I008675/1]
Transport of proteins across and into membranes is a fundamental process in biology. Recent studies have shown that the diffusion of arginine residues limits pre-protein transport, while lysine can be transported across membranes in its neutral form. These findings have implications for understanding the mechanism of protein secretion and suggest a potential role of proton-motive force in aiding transport.
Transport of proteins across and into membranes is a fundamental biological process with the vast majority being conducted by the ubiquitous Sec machinery. In bacteria, this is usually achieved when the SecY-complex engages the cytosolic ATPase SecA (secretion) or translating ribosomes (insertion). Great strides have been made towards understanding the mechanism of protein translocation. Yet, important questions remain - notably, the nature of the individual steps that constitute transport, and how the proton-motive force (PMF) across the plasma membrane contributes. Here, we apply a recently developed high-resolution protein transport assay to explore these questions. We find that pre-protein transport is limited primarily by the diffusion of arginine residues across the membrane, particularly in the context of bulky hydrophobic sequences. This specific effect of arginine, caused by its positive charge, is mitigated for lysine which can be deprotonated and transported across the membrane in its neutral form. These observations have interesting implications for the mechanism of protein secretion, suggesting a simple mechanism through which the PMF can aid transport by enabling a 'proton ratchet', wherein re-protonation of exiting lysine residues prevents channel re-entry, biasing transport in the outward direction.
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