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1784: CRISPR-Cas Transposase Part I

Closed since about 6 years ago

Intermediate Overall Prediction

Summary


Created
January 09, 2020
Expires
Max points
100
Description

Fold this transposase protein from a CRISPR-Cas complex! CRISPR-Cas is a mixed complex of RNA and proteins, which work together to make a very precise cut in a cell's DNA. Scientists recently discovered a variant of CRISPR-Cas that coopts a new protein called a transposase. In addition to cutting DNA, the transposase also allows precise insertion of new material into a target DNA strand. This new variant could lead to more efficient gene editing with CRISPR-Cas! New cryoEM experiments have shed some light on the transposase structure, which was previously unknown.



We're asking Foldit players to help solve how this transposase protein folds! The transposase is a large 400-residue protein, so this puzzle only includes the first half of the protein, and we will post the second half of the protein in a follow-up puzzle. Later, we'll post additional puzzles with cryoEM density for the transposase protein!



Sequence:

MFLQRPKPYSDESLESFFIRVANKNGYGDVHRFLEATKRFLQDIDHNGYQTFPTDITRINPYSAKNSSSARTASFLKLAQLTFNEPPELLGLAINRTNMKYSPSTSAVVRGAEVFPRSLLRTHSIPCCPLCLRENGYASYLWHFQGYEYCHSHNVPLITTCSCGKEFDYRVSGLKGICCKCKEPITLT

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Comments


bkoep Staff Lv 1

We were able to kick the servers yesterday and got the scoreboards up momentarily, but it looks like they've fallen off again. Still trying to figure out what the issue is…

bkoep Staff Lv 1

We don't like to include the Building Blocks on prediction puzzles, because we don't want to bias players towards structures that look like "designed proteins."

The Building Blocks are very useful for design puzzles, because designs created with only these loops tend to be more stable. However, natural proteins are much more varied than designed proteins, and are likely to have longer, unstructured loops. If we enabled the Building Blocks on prediction puzzles, we're afraid Foldit players (especially new players) would rely on them too much, and would not explore different kinds of loops.

On the other hand, the Rebuild tool is available! The Rebuild tool uses random fragment-assembly to create a wide diversity of loops. These loops tend to decrease the stability of designed proteins (which is why Rebuild is disabled in design puzzles). But Rebuild is good for sampling large, unstructured loops that tend to show up in natural proteins.

jeff101 Lv 1

Puzzle 1784's 188 amino acid protein contains
9 cysteines. Do any of these cysteines form
disulfide bonds? If so, are they disulfide
bonds within Puzzle 1784's protein or do they
connect this 188 amino acid protein to another
protein? Should we put all 9 of these cysteines
on the surface of Puzzle 1784's 188 amino acid
protein?

Thanks!

frood66 Lv 1

we only have half the protein - so no way of knowing. Personally I still have one bridge - tho I started with more

bkoep Staff Lv 1

Good question! We don't expect any disulfides to form in this protein, since it is found within the cell.

(In the reducing environment of the cytoplasm, protonated reduced cysteine is more stable than disulfide-bonded cysteine.)

Anfinsen_slept_here Lv 1

Not to split hairs, but it is kinda wrong to call a reduced cysteine "protonated". It's not that the cysteine is just protonated relative to being in a disulfide; each cys has gained both a proton and an electron compared to the oxidized S-S state. Ok i am splitting hairs, but i cringe a little when acid/base chemistry gets conflated with redox chemistry.

My pickiness for precise language is beside the point. Thank you for clarifying that this protein is likely in a reducing environment

bkoep Staff Lv 1

And you are right to call me out on it! This is sloppy language on my part, and liable to cause confusion. Protonation and reduction are very different chemistries, and we're not doing anyone favors by conflating the two!