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Beyond genes: Lipid helps cell wall protein fold into proper shape

A protein that provides a vital passage through a bacterium's outer cell wall will misfold and malfunction if that wall is built of the 'wrong' material, scientists at The University of Texas Medical School at Houston report in a finding that has long-term implications for understanding diseases caused by misfolded proteins such as cystic fibrosis, Alzheimer's disease, and mad cow disease.

The paper in today's Journal of Biological Chemistry by Professor of Biochemistry and Molecular Biology William Dowhan, Ph.D., and colleagues shows that phospholipids, which make up the permeable barrier of cell membranes, play a direct role in the folding of membrane proteins ?proteins that penetrate the membrane or bind to either side of it.

"What we've demonstrated again is that it's not just a membrane protein's genetically determined sequence that dictates how it folds so that it can function properly. Its lipid environment also plays a role," Dowhan said. "People used to assume that specific lipids made no difference."

In the JBC paper, Dowhan and colleagues looked at how a protein called GabP, which transports an amino acid across the membrane of the bacterium E. coli, is affected by the presence of a phospholipid named phosphatidylethanolamine, or PE for short.

Phospholipids, unlike their fatty acid and cholesterol cousins, include a phosphate group that spurs them to form a bilayer with water-friendly outer layers sandwiching an impermeable water-unfriendly inner layer that defines the outer surface of cells. Transport of nutrients and waste material across the cell membrane is then governed by the specific proteins associated with it.

In a strain of E. coli lacking PE, the GabP protein misfolded, with two areas of the protein inverting from their normal structure. The PE-lacking protein's amino acid transfer rate plummeted to nearly zero, falling 99 percent compared to the transfer rate in unaltered E. coli with PE.

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Source:University of Texas Health Science Center at Houston


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