1797: CRISPR-Cas Transposase Part II: Electron Density

Closed since about 6 years ago

Summary

• Created: February 07, 2020
• Expires: February 14, 2020 at 23:00 UTC
• Max points: 100

Description

Fold the transposase protein into a density map! This is a followup to Puzzle 1787: CRISPR-Cas Transposase Part II, now with a cryo-EM density map! Players may load in previous work from Puzzle 1787.



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 residues from the second half of the protein. Likewise, the provided density corresponds to only this half of the transposase protein.



Sequence:

GHEAACTVSNWLAGHESKPLPNLPKSYRWGLVHWWMGIKDSEFDHFSFVQFFSNWPRSFHSIIEDEVEFNLEHAVVSTSELRLKDLLGRLFFGSIRLPERNLQHNIILGELLCYLENRLWQDKGLIANLKMNALEATVMLNCSLDQIASMVEQRILKPNRKSKPNSPLDVTDYLFHFGDIFCLWLAEFQSDEFNRSFYVSRW

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Comments

[Susume]

The density on this one is in strange flat layers, like it's been skewed somehow. The parts that do look kinda helixy also look like they have been squashed diagonally.

[Bautho]

That's a problem with cryo-EM. It looks like the transposase is very flexible in the overall map of the CRISPR complex. In the corresponding paper, they write, that they have improved the density by masked refinement, but did not publish the map…

[Bruno Kestemont]

Do we see only half the density to fit half the protein, or do we get the whole cloud ?

[Bruno Kestemont]

I've the impression that this one is not for advanced players but only for future Nobel prices ;)

[bkoep]

The density here is only half of the transposase density, corresponding to this half of the transposase sequence.

(Puzzle 1794 included the other half of the density, with the other half of the sequence.)

[jeff101]

If you make sequels to the puzzle series 1784/1794 or 1787/1797,
please let solutions from all previous puzzles in each series
work in their sequels too. If you give us different ED Clouds,
please keep the same coordinates so that if we positioned protein
parts correctly in the previous puzzles, we won't have to adjust
them in the sequels. Please also copy all ED dots from 1794 and
1797 solutions into these puzzles' sequels so that we won't have
to lay out all these ED dots again.

Thanks!
Jeff

[bkoep]

We'll be sure to allow sharing in sequel puzzles so that you can continue with your previous work! I'm not sure if the ED dots can be transferred from puzzle to puzzle…