Reason for body's response to borrelia discovered

Inside a cell it is so crowded that a certain protein from borrelia winds up being crunched. From having been like an oblong rugby football, it gets bent and then collapses into a lump. At this point a previously hidden part appears, known to trigger the formation of antibodies. This explains how Borrelia can be diagnosed, a process that was previously unknown.

Congestion in the cell environment forces the protein V1sE, which exists in borrelia bacteria, to change shape. Like a jack-in-the-box, an antigen- a substance alien to the body -then pops up, prompting the body to start producing antibodies. It is precisely the prevalence of these antibodies that physicians often use to diagnose borrelia.

Until today, we have had no knowledge of how these antibodies are produced, since the antigen is hidden in the original form of the V1sE protein.

"We suspect that the changes in the shape of the protein are nature's own origami to control what functions the protein should have in specific circumstances. In this way different parts can be exposed, roughly as in the jumping fleas made of folded paper that children play with," says Pernilla Wittung-Stafshede, who was recently named professor of biological chemistry at Umeå University in Sweden.

Together with colleagues from the U.S., she has published these findings in the U.S. journal Proceedings of the National Academy of Sciences.

How proteins fold and change their shape has been studied intensively for many years in vitro, but in these studies primarily diluted water solution has been used. Pernilla Wittung-Stafshede stresses that it makes a big difference to study a cell environment.

"A cell is not a 'sack of water.' It's a thick as a gelatin, and the total number of large molecules in a cell can correspond to up to 40 percent of its total volume. This means that proteins have less room to fold an function in," explains Pernilla Wittung-Stafshede.

The crowdedness of a cell thus entails that the form and function of proteins can be affected.

"This means in such cases that it if it was possible to modulate the congestion in the cell, it could constitute a precision tool for manipulating the shape of a protein. What other proteins might have different functions if we crunched them together? With such a tool, we might be able to turn specific activities and signals on or off in proteins. We speculate that this could be used in the future to affect the course of various diseases, for example," she explains.

The study is the first to show that crowdedness in the cell can entail shape changes in a large, biologically relevant protein. The studies were carried out with the aid of computer simulations and laboratory experiments.

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