Proteins are more dynamic than scientist originally realized
The static environment needed to study protein structure let scientist long believe that proteins were less dynamic than they actually are.
While, reading background information for my book about protein folding and how AlphaFold solved that problem, it struck me, our view of what we think proteins are has changed significantly over the years. For a long time, we viewed proteins as more or less static molecules. And although scientist have known since the determination of the structure of hemoglobin by Max Perutz, that a protein can have multiple structures depending on their environment. Like and active and a non-active state. But they did not stand still by what this meant. As the structures they solved using X-ray crystallography were static.
But over the years, with the characterisation of more and more proteins, this view of proteins behaving as more or less static molecules started to change. I think the first real shift appeared when animations depicting the working of proteins occurred. These showed proteins, for example, as package delivery guys that trudge over the cytoskeleton highway of the cell. Visualising the structural changes a protein cycles through while doing its job, even if it is only switching between two options.
This visualised the dynamics of proteins. Although, of only a small subset. Because at the time it was impossible to even guess the shape for most proteins. Then a few years ago AlphaFold came along. Suddenly there was a prediction for everyone’s favourite protein, and then some. Now we could not only see the shape of proteins that sat still long enough for structure determination, but also of those that did not.
Those extremely dynamic, or the so called intrinsically disordered proteins, suddenly looked like strands of spaghetti thrown randomly on a plate. AlphaFold could not figure out how they folded so they stayed unfolded.
Since then, there has been lots of talk about how databases like those of AlphaFold predicted protein structures only give one possible structure. And that this is a big shortcoming. It did accelerate our awareness that most proteins are highly dynamic molecules. And that is like Dr Katja Luck who studies protein-protein interactions, says maybe one of AlphaFold’s greatest achievements. Especially when you consider it is something that AlphaFold can’t do showing the dynamics of protein structures.
Back to the folding problem
This also intrigues me. Because part of the protein folding problem is that scientist believed that proteins quickly find their optimal structure. Within minutes they believed. Scientist therefore like to know how proteins can find their optimal structure so quickly. Especially as random sampling is not the answer.
But as the spaghetti structures of intrinsically disordered proteins illustrate, not all proteins find their optimal structure right after synthesis. Sometimes they swim trough the cell until they come across say another protein when they snap into shape. Like how fans flock towards a popstar. The proteins do their thing and subsequently let go and unwind again.
The answer to the protein folding problem therefore need to take into account those intrinsically disordered proteins and all other protein dynamics. A particular structure can be optimal in one condition, but not in another, forcing a protein to shift shapes. When talking to scientist who focus on solving the protein folding problem, this is definitely something I will be asking about.
Other stories I came across this week
An orchid supercharging its growth
I read how the orchid Oreorchis patens sometimes steals from its symbiotic fungi, and it’s all the healthier for it. It only does so when growing near nutrient rich decaying wood. In those places it tops up its sugars that it produces via photosynthesis with sugars, and other nutrients it can steal from fungi decomposing the wood. Is the orchid growing anywhere else, then it does partner up with fungi, but treats them like symbiotic partners, trading sugars for water and nutrients.
10 new sponge species identified
After looking in lots of nooks and crannies of their reef, Hawaii scientists discovered 10 new sponge species. And that is a lot, considering that their patch of reef is well studied. Moreover, sponges are notorious difficult to study. They have s short lifespan, so they might be there one moment and gone the next.
Booming plant genomics
Plant genomics is booming. More and more plants have their genomes sequenced. Not only those that are currently growing on our planet, but also those that in herbariums. And this helps scientists deciphering how plants respond to environmental changes. It is this knowledge that scientists tap into when future proofing our crops.