1964: Unsolved Huge Cryo-EM Density: Beet Virus

Closed since almost 5 years ago

Summary

• Created: March 04, 2021
• Expires: March 18, 2021 at 18:00 UTC
• Max points: 100

Description

We are very excited about this puzzle, because our collaborators who provided us with the 4 structures from Foldit's 2019 cryo-EM paper have been unable to solve this cryo-EM structure.
This will not be easy, because the full density has 46 symmetric monomers and we can't cut out a single copy of density for you (since we don't know the structure). Instead, we've sliced off a quarter of the entire density, which our collaborators estimate should be ~10 monomers. So keep this in mind, as we are only providing you with a single monomeric chain to fold. More details and pictures in the puzzle comments!

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Comments

[beta_helix]

This 3.5Å cryo-EM map is the nucleocapsid of a plant virus and contains a long RNA molecule that follows the helical symmetry.
Therefore, some of the electron density that you have been given should not be filled with protein.

Sequence:
MSSEGRYMTWKDMSHNKFMTDRWARVSDVVSVIKQSHAMDLSKAANLS
IIKTALAGLGSGWSDSNPFVSPMTRFPQTLTMYGALVLYVNLSDPEFA
LIMTKVNTLTDSGLADNASANVRRDVVSGNKAESSGKTAGTNENSAYT
LTVSLAGLAQALRLEELMWTRDKFEDRFKLPWTPVQGRTSPPGQ

The full cryo-EM map has 15.25 monomers per helix turn (side-view shown in image below).
We didn't want to provide you with this full map, as it fits ~46 monomers, so instead we have given you a large "slice" that should contain around 10 monomers (the blue "donut slice" in the top-view image at the very bottom).

We obviously do not know the precise details, because the only way to perfectly trim the cryo-EM map down to a single chain would require solving the structure! We know this puzzle will not be easy, which is why we are providing you with 14 days to work on it… good luck!

[Susume]

Are all the monomers assumed to have the same shape and a similar place in the donut? Like if one of them contacts the inside of the donut, then all of them contact the inside of the donut in the same way?

[beta_helix]

From what we know about this protein: most likely yes, they are all the same pose.

[jeff101]

"This 3.5Å cryo-EM map is the nucleocapsid of a plant virus and 
contains a long RNA molecule that follows the helical symmetry.
Therefore, some of the electron density that you have been given 
should not be filled with protein."

Does this mean some of this puzzle's ED cloud is due to RNA?
Should we expect to see odd non-protein ED in its cloud?

[LociOiling]

Jpred was in a good mood today, so here's the results page for this protein: puzzle 1964 prediction

That link will probably expire at some point, I think the predictions have only a finite shelf life.

The first match is to a sequence known as UniRef90_G1BIV2, which gets you to a paper Beet soil-borne mosaic virus RNA-3 is replicated and Beet soil-borne mosaic virus RNA-3 is replicated and encapsidated in the presence of BNYVV RNA-1 and -2 and allows long distance movement in Beta macrocarpa in the presence of BNYVV RNA-1 and -2 and allows long distance movement in Beta macrocarpa from 2009.

My main takeaways so far are 1) "encapsidated" is a word, 2) Beta macrocarpa is a scientific name for a type of beet, and 3) that paper has a really long title.

(Maybe we'll change our group name to "Beet Folders".)

[beta_helix]

That is indeed what we expect.

[beta_helix]

Thanks LociOiling,

If your team solves this structure, the Beta Folders should totally change their name to Beet Folders! :-P

[frood66]

do u guys at Foldit think this ed will actually help? or are u just looking for a lucky pose.?

no I am not being rude….I simply do not understand the point of this puzzle - nor the use of an ed.

[Susume]

This is not the same virus (not even similar sequence I don't think), just one that has similar architecture to help folks view it.
https://www.rcsb.org/3d-view/1CGM
Like our puzzle, this virus forms a hollow cylinder with about 15-16 copies of the protein making one full turn, then continues into another turn - it's a very flat helix that ends up looking kind of like a layer cake. The protein's job is to pack around the RNA to protect it - you can see the RNA (on my screen it's green) tucked in between the protein layers.

Every copy of the protein has to touch the inner surface of the donut - which means it's pretty crowded in there! There's only room for each protein to form one loop in the center, then it has to head back out toward the outer surface. If you can find the identical loops on the inner surface in our puzzle ED, you can mark them with colored dots to help you decide which protein copy to follow (I used red for all the ones I didn't want and green for the one I picked).

Similarly, every copy has to take up about 1/16 of the outer donut surface in its 'cake layer', so you can look for repeated shapes in the outer layer to mark. Finally, if you look straight down through the donut in this sample virus, you can see that the 'wedges' formed by the individual proteins are not straight-sided triangles but sort of crescent-shaped - I don't know if that's true in our puzzle, but it's something to look for.

[beta_helix]

I believe that this ED will help, but indeed it will not be easy (hence the Expert difficulty).

Since the ED cloud boosts your Foldit score if it matches your model, you can think of it as:
The highest possible Foldit score on this puzzle if you ignore the ED is some number X,
but the highest possible Foldit score on this puzzle (if you are able to match the ED correctly) is going to be a lot higher than X.