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Biological Chemistry

Floppy linkers direct bacterial proteins

Length and disorder of the linkers are key to sorting between inner and outer membranes

by Celia Henry Arnaud
August 8, 2021 | A version of this story appeared in Volume 99, Issue 29

Two lipoproteins with long, disordered linkers.
Credit: Nat. Chem. Biol.
In Escherichia coli, many lipoproteins in the outer membrane have long, disordered linkers (magenta). Shown here are RcsF (left), which acts as a stress sensor, and Pal (right), which is involved in outer-membrane constriction during cell division.

Gram-negative bacteria such as Escherichia coli have a cell envelope consisting of an inner and outer membrane. About one-third of all E. coli proteins are localized in the cell envelope, with some proteins associated with the inner membrane and others with the outer membrane. The process by which this sorting happens is poorly understood. Jean-François Collet of Université catholique de Louvain and coworkers have now found that in E. coli, half the lipoproteins located in the outer membrane have a long, intrinsically disordered linker attached to their N terminus (Nat. Chem. Biol. 2021, DOI: 10.1038/s41589-021-00845-z). Both the length and the disorder of the linker help determine where the proteins end up, the researchers find. When synthetic linkers replace the natural ones, the proteins are still routed to the outer membrane if the synthetic linkers are unstructured and have more than 22 amino acids. With linkers that were only 10 or 18 amino acids long or had α-helical structure, the proteins instead accumulated in the inner membrane. The researchers don’t yet know whether disordered linkers play a similar role in other gram-negative bacteria. If so, the process of lipoprotein sorting could be a new target for antibiotics, the researchers say.


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