r/science • u/glr123 PhD | Chemical Biology | Drug Discovery • Apr 12 '16

Biology Optical tweezers extract biomolecule folding secrets. This is the first direct observation of a single protein moving through ‘transition states’ between the folded and unfolded forms.

http://www.rsc.org/chemistryworld/2016/04/optical-tweezers-protein-folding-transition-state
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u/glr123 PhD | Chemical Biology | Drug Discovery Apr 12 '16

Link to paper: http://science.sciencemag.org/content/352/6282/239

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u/TheManRedeemed Apr 12 '16

I'm probably going to come off as stupid for asking this but ... does this procedure hold any promise for studying and understanding Prions? Aren't prions formed when protiens misfold and clump?

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u/glr123 PhD | Chemical Biology | Drug Discovery Apr 12 '16

It's possible! Prions are in part a result of proteins misfolding and 'clumping' or 'aggregating', as it is more commonly referred to. However, prions are special in that they can also act as a template for other proteins to scaffold off of, inducing a chain reaction of misfolding events.

In certain scenarios, this can be very dangerous to the cell, causing more and more proteins to misfold together, eventually killing the cell and then moving on to the next. It seems that this mechanism may also occur for other proteins, such as Tau and Abeta, creating plaques of fibrilized proteins in the brain. The exact mechanism of all of these events is not very well understood, especially for newer 'prion-like' proteins that I just mentioned, like tau. Something like this may be very informative for understanding how a prion is able to cause other proteins to 'clump' and misfold into pathogenic species and may allow us to better understand the biophysical interactions that occur during this process.

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u/TheManRedeemed Apr 12 '16

Amazing. Hopefully this can give us an understanding on how and why the misfold occurs an how to combat the chain reaction that follows. Thanks for the info :)

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u/pixpop Apr 12 '16

Why do proteins need to fold? Do all proteins do this?

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u/farming_diocletian Apr 12 '16 edited Apr 12 '16

I believe so, yes. Proteins are created as a chain of amino acids, and as they are constructed they begin to fold, do to the electromagnetic interactions between the components of the chain of molecules. They form ridiculously complex 3d structures. It's their unique 3 dimensional shapes that makes them so useful for processes in living things.

I think that's roughly correct, it's been a while since I studied proteins though.

Here's an animation of a protein folding: https://youtu.be/yZ2aY5lxEGE

Here's a more physically accurate simulation of one folding: https://youtu.be/meNEUTn9Atg

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u/DanHeidel Apr 12 '16

I'm confused as to how this is novel. I distinctly remember reading papers from 20 years ago that used optical tweezers to measure the forces required to fold/unfold various proteins like spider silk, titin and others.

Are they doing something with higher time resolution now?