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1952: BAM Complex with Electron Density

Closed since over 1 year ago

Advanced Overall Prediction Electron Density

Summary


Created
February 04, 2021
Expires
Max points
100
Description

This protein is part of a large protein complex with multiple subunits, which was recently solved by cryo-electron microscopy (cryo-EM) at 4.2A resolution. Unfortunately, the solved structure could really use some work so we are hoping you can improve the structure. One end of the unfolded chain is close to its correct position in the electron density, but the rest of the chain is completely extended and will need to be refolded to fit in the density cloud. Keep in mind that this will not be easy, as 4.2A resolution results in a challenging electron density cloud to work with! The starting structure includes several locked protein fragments in the electron density cloud. These are additional proteins that are also present, and are expected to make interactions with the final folded structure. Good luck!

***More details about the native structure in the puzzle comments***

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Comments


Susume Lv 1

How confident are you that the locked fragments are placed correctly? They don't seem to match the density super well.

frood66 Lv 1

I am away for 10 months or so…….it feels like home to see the old issues have still to be addressed :)
but I guess that is progress?

Susume Lv 1

I got this SS from psipred (translated into jpred format just 'cause I like that better; H=helix, E=sheet):
--71--------81--------91-------101-------111-------121-------131-------141-------151--- ERVVYRPDINQGNYLTANDVSKIRVGMTQQQVAYALGTPLMSDPFGTNTWFYVFRQQPGHEGVTQQTLTLTFNSSGVLTNIDNKPAL ----------------HHHHHH------HHHHHHHH-------------EEEEEEEE------EEEEEEEEE-----EEEEE-----

LociOiling Lv 1

This puzzle kind of strains AA Edit/SS Edit/print protein, since it has protein chains A through I. The dialogs in these recipes may be too tall to fit on some screens. SS Edit is probably the best bet of the three size-wise. I'll work on scrollable dialogs to fix that, but in the mean time here's the takeaway.

Chain I is the foldable part, while chains A through H are anchored somewhere in the cloud.

The chain I AA sequence is:

ervvyrpdinqgnyltandvskirvgmtqqqvayalgtplmsdpfgtntwfyvfrqqpghegvtqqtltltfnssgvltnidnkpal

Trusty Jpred finds a number of exact PDB matches.

Chain I in the Foldit puzzle exactly matches chain E in these PDB entries:

5ayw 5d0o 5d0q 5d0q 5ekq
5ljo 6lyq 6lyr 6lys 6lyu
6sn9 6sob 6soj 6v05

As is often the case, some interpolation is necessary to get the numbering schemes to line up.

In Foldit, the foldable chain I starts at segment 68, and runs to segment 154, for a length of 87 segments.

Looking at 6v05 in JMol or the PDB viewer of your choice, the first five residues are missing for chain E. The model starts with arginine as residue 29, which corresponds to segment 73 in Foldit.

So for 6v05 at least, the rule is to add 44 segments to what you see in your PDB viewer to get the equivalent Foldit segment.

No guarantees on my work, but here's the secondary structure for chain E from PDB 6v05:

LLLLLLLLEEELLLLHHHHHHHLLLLLHHHHHHHHHHLLLLLLLLLLLEEEEEEEEELLLLLLEEEEEEEELLLLLLLLEEEEELLL

beta_helix Staff Lv 1

The N-terminus is in the general vicinity of the cloud.

It is probably closer to the little isolated clouds of density that are at the edge of that region (they look like 4 islands breaking off).

I'm sorry I can't post a photo (thank goodness the new website is coming!)

We just didn't want to have you search the entire cloud for the N-terminal end of the density.

infjamc Lv 1

Given the existence of PDBs that are exact matches, to what extent are people allowed to consult publicly available external sources like 6v05?

According to https://fold.it/portal/communityrules#cheating , copying is allowed for primary and secondary structures, but not tertiary and quaternary structures. But what about "Level 2.5" approaches, such as noting that two specific beta strands go together (while NOT going as far as to attempt a full duplication down to the residue / angle level)?

Also, could there be an option to designate an existing structure as "evolved from external sources," i.e. voluntarily exclude it from soloist competition for the sake for fairness (due to usage of the "Level 2.5" approach described above, etc.)? Alternatively, could the known native be provided as a "global evolver solution" (i.e. allow everyone to load in directly into Foldit) order to level the playing field?

jeff101 Lv 1

<pre>In Puzzle 1952, we have several small locked fragments from segments 1-67 and one long continuous unlocked fragment from segments 68-154.

None of the 154 segments are mutable,
but many have more than one rotamer,
so wiggling sidechains or shaking for
both segments 1-67 and segments 68-154
should affect the score. Nevertheless,
rebuild, remix, or wiggle backbone should
only alter the score for segments 68-154.

Viewing with cpk, stick, all hydrogens, & all sidechains
shows that residue 68 (e=glutamate) ends with NH3
while residue 154 (l=leucine) ends with COO.
Does this mean the N-terminal of our unlocked fragment
is at residue 68 while the C-terminal is at residue 154?

Does Puzzle 1952 have any constraints holding the
N-terminal of segments 68-154 at its desired location?
Can you please describe the N-terminal's desired
location using distances between glu68's NH3 nitrogen
and several nearby backbone atoms on the locked
segments in Puzzle 1952?

Finally, does the ED Cloud for Puzzle 1952 contain
any other protein fragments besides the ones given
to us as segments 1-154 in this puzzle?

Thanks!</pre></code>

beta_helix Staff Lv 1

As LociOiling discovered, the chain we gave you to fold into the density is 6LYU chain E:
https://www.rcsb.org/sequence/6LYU#E
which is the shortest chain from the 6LYU complex: https://www.rcsb.org/structure/6LYU
(You can see that we fixed segments of the other chains that are closest to chain E)

We want to emphasize that we believe the deposited structure has errors, because you can see how poor the PDB validation scores are (particularly the clash scores on page 2):

Lastly, we hope to have future ED puzzles that will be blind (where the native will not be available) so we want to encourage you to practice folding without the native. This, of course, is difficult when anyone can look up the PDB.

Perhaps we can suggest folding it at first with just the given density, and then looking up the reference structure in the last few days of the puzzle?