Reference - Detail
|Author||Gray AN, Henderson-Frost JM, Boyd D, Sharafi S, Niki H, Goldberg MB.|
|Title||Unbalanced charge distribution as a determinant for dependence of a subset of Escherichia coli membrane proteins on the membrane insertase YidC.|
UNLABELLED:Membrane proteins are involved in numerous essential cell processes, including transport, gene regulation, motility, and metabolism. To function properly, they must be inserted into the membrane and folded correctly. YidC, an essential protein in Escherichia coli with homologues in other bacteria, Archaea, mitochondria, and chloroplasts, functions by incompletely understood mechanisms in the insertion and folding of certain membrane proteins. Using a genome-scale approach, we identified 69 E. coli membrane proteins that, in the absence of YidC, exhibited aberrant localization by microscopy. Further examination of a subset revealed biochemical defects in membrane insertion in the absence of YidC, indicating their dependence on YidC for proper membrane insertion or folding. Membrane proteins possessing an unfavorable distribution of positively charged residues were significantly more likely to depend on YidC for membrane insertion. Correcting the charge distribution of a charge-unbalanced YidC-dependent membrane protein abrogated its requirement for YidC, while perturbing the charge distribution of a charge-balanced YidC-independent membrane protein rendered it YidC dependent, demonstrating that charge distribution can be a necessary and sufficient determinant of YidC dependence. These findings provide insights into a mechanism by which YidC promotes proper membrane protein biogenesis and suggest a critical function of YidC in all organisms and organelles that express it.
IMPORTANCE:Biological membranes are fundamental components of cells, providing barriers that enclose the cell and separate compartments. Proteins inserted into biological membranes serve critical functions in molecular transport, molecular partitioning, and other essential cell processes. The mechanisms involved in the insertion of proteins into membranes, however, are incompletely understood. The YidC protein is critical for the insertion of a subset of proteins into membranes across an evolutionarily wide group of organisms. Here we identify a large group of proteins that depend on YidC for membrane insertion in Escherichia coli, and we identify unfavorable distribution of charge as an important determinant of YidC dependence for proper membrane insertion.
|MeSH||Cell Membrane / chemistry Cell Membrane / genetics Cell Membrane / metabolism Escherichia coli / chemistry Escherichia coli / enzymology* Escherichia coli / genetics Escherichia coli / metabolism Escherichia coli Proteins / metabolism* Membrane Proteins / chemistry* Membrane Proteins / genetics Membrane Proteins / metabolism Membrane Transport Proteins / metabolism* Protein Transport|
|Prokaryotes E. coli||JW0423 JW0845 JW0846 JW3716 JW2187 JW0826 JW3789 JW0619 JW0590 JW0870 JW0421 JW2375 JW2364 JW5012 JW0543 JW2436 JW2974 JW0581 JW0468 JW3427 JW5494 JW3421 JW0654 JW5061 JW0629 JW1844 JW1655 JW2283 JW0841 JW2653 JW2022 JW1264 JW1358 JW2032 JW3991 JW3540 JW0006 JW0281 JW0699 JW0769 JW0770 JW0771 JW0777 JW0798 JW0944 JW1015 JW1336 JW1437 JW1438 JW1480 JW1593 JW1660 JW1822 JW1903 JW1942 JW2062 JW5391 JW2488 JW2643 JW2954 JW3035 JW3060 JW3074 JW3075 JW5701 JW3586 JW5388 JW2527 JW2641 ASKA library|