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Comment by philsnow | Hacker News Reader

How is it that this MYC protein “has no structure”?

As far as I know, protein structure comes out naturally during transcription, as the various amino acids are attracted to each other or repel each other. The mechanisms of protein interaction depend on their three-dimensional shapes! If a protein has no structure, how can it serve a function?

Of course I’m not suggesting that they’re wrong in any way, this is clearly a hole in my understanding of proteins that I wasn’t able to plug with google.

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There are proteins known as "Intrinsically Unstructured Proteins" or "disordered" proteins. That function with no fixed configuration. Typically a good way of thinking about them is an ensemble of transient more common states, where things like post translational modification alters how long and which conformations the protein visits. The other replies you've gotten are inaccurate and about 15+ years out of date in thinking about protein structure.

Think of a roiling noodle where sections or the whole thing linger in certain shapes and configurations longer than in other positions.

This paper can give you a better idea about MYC specifically https://europepmc.org/article/MED/22457068

If you want to know more about disordered proteins in human DisProt is a good place to start https://disprot.org

The other replies that are "about 15+ years out of date" do cite literature that is more than 10 years newer than your references, though...

> The other replies you've gotten are inaccurate and about 15+ years out of date in thinking about protein structure.

I do not believe the case, speaking as one of the others replies, and having reviewed the others. But since you do, could I request the extra work of some pointers to the inaccuracies?

NMR-driven descriptions of protein structure flexibility are far more than 15 years old, and common in all graduate bio courses since the 90s, so if I'm perpetuating some sort of inaccuracy I'd really like to know so I can stop.

The structure comes from having a consistent configuration of the bond angles. Most proteins are fairly ordered, and even if they wiggle around a bit and are jiggly, they fold back into the same shape.

However, it's not uncommon to have disordered or unstructured parts of a protein, that have no consistent shape, and are completely moveable.

MYC is kind of on the extreme end of this. There's just one domain of the protein with a consistent structure, and the rest kind of conforms to the other proteins it binds to, or wiggles about.

This may not be the best paper on it, but it does review a bit of the unstructured nature of MYC among lots of other stuff too:

https://www.cell.com/trends/cell-biology/pdf/S0962-8924(22)0...

I think what they mean is that the protein does not have a single conformation that it adopts and then remains in. It's fairly common when solving the x-ray crystal structure of a protein to find that some regions of the molecule are just disordered and don't have a clear shape. If you're asking what is going on at the atomic level, the answer would be that the protein is continuously changing shape as it flops around its solution environment. Of course, if you could freeze time at any one instant, you would find that every atom has defined coordinates and therefore the overall molecule has some shape. The point is just that it's dynamic.

That's how I interpreted the article, but I don't have any specific knowledge of this protein.

There are also chaperone proteins that help in the folding process: https://en.m.wikipedia.org/wiki/Chaperone_(protein)

Proteins have moving parts. Some function like turnstiles, others walk along microtubes. "Intrinsically disordered proteins" is a key word that might help. Biochemistry is like a stochastic soup sometimes.

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