Monday, April 17, 2017

disorder turns 20

Open archives

Today I’ll exceptionally present a feature from the archives that was published in Chemistry World, not in Current Biology.

The occasion is that today is the 20th anniversary of one of my favourite and most impactful papers from my research career, even though it did not result from actual research I did.

What happened back in 1997 was that my friend and colleague Kevin Plaxco happened to know about a paper from molecular biologists coming out on a weird mechanism controlling the growth of the tail (flagella) that certain bacteria use to swim. The tail is a hollow tube, and while it is being built, a certain signalling protein escapes through the tunnel and is lost to the cell. When the tube is finished and closed, the protein accumulates in the cell and thereby signals that no more bricks are needed to extend the tunnel.

What Kevin noticed was an aspect that left the molecular biologist authors of the original paper gloriously uninterested – namely the fact that to carry out its biological signalling function this protein needed to be an unfolded, 1D thread, as opposed to a complex 3D structure as all functioning proteins were supposed to be according to the prevailing dogma that sequence determines structure determines function.

So Kevin told me about this and suggested to write a News & Views piece for Nature, which we did, and which came out 20 years ago today. At the time there were only two or three other examples of “intrinsically disordered” proteins that are functional while unstructured. Mostly the evidence relied on NMR spectroscopy, which invites the objection that maybe the researchers didn’t get the conditions quite right and maybe the protein would be more orderly if they did x instead of y.

The beauty of the system we discussed was that the biological function of the protein made it absolutely necessary to unfold, as it wouldn’t fit through the tube in its folded state.

Anyhow, this turned out to be the beginning of a whole new research field which grew quite impressively over the next years, so in 2010 I had the pleasure of attending a research conference at Barcelona that was all about intrinsically disordered proteins.

And summarising what I learned at this conference, I wrote a feature about the topic which appeared in 2011, and which is freely accessible:

Anarchy in the proteome
Chemistry World, August 2011, pp 42-45
FREE access to PDF file

screenshot of our 1997 News & Views (PDF - if you hit the paywall, try this)

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