Placeholder image of a protein
Icon representing a puzzle

2439: Electron Density Reconstruction 85 (use trim tool)

Closed since almost 2 years ago

Novice Overall Prediction Electron Density

Summary

Created
April 04, 2024
Expires
Max points
100
Description

This is a structure that's been published previously, but we think it has some issues that need revision. This is a cryo-EM structure of a fibril isolated from a patient with Multiple System Atrophy. Although the structure in general could use work, we're especially suspicious of the positioning of the segment K80. Since it's a fibril, there's several copies of the protein stacked together here, making it a large puzzle, and so the trim tool is highly recommended.

Top groups

  1. Avatar for Anthropic Dreams
    1. Anthropic Dreams
    100 pts. 61,805
  2. Avatar for L'Alliance Francophone 2. L'Alliance Francophone 52 pts. 61,533
  3. Avatar for Contenders 3. Contenders 24 pts. 61,521
  4. Avatar for Go Science 4. Go Science 10 pts. 61,484
  5. Avatar for Australia 5. Australia 4 pts. 61,351
  6. Avatar for Marvin's bunch 6. Marvin's bunch 1 pt. 61,156
  7. Avatar for FamilyBarmettler 7. FamilyBarmettler 1 pt. 60,944
  8. Avatar for VeFold 8. VeFold 1 pt. 60,657
  9. Avatar for Kotocycle 9. Kotocycle 1 pt. 59,506
  1. Avatar for LociOiling
    1. LociOiling Lv 1
    100 pts. 61,805
  2. Avatar for BackBuffer 2. BackBuffer Lv 1 94 pts. 61,605
  3. Avatar for christioanchauvin 3. christioanchauvin Lv 1 87 pts. 61,533
  4. Avatar for Bletchley Park 4. Bletchley Park Lv 1 81 pts. 61,521
  5. Avatar for drjr 5. drjr Lv 1 76 pts. 61,450
  6. Avatar for NinjaGreg 6. NinjaGreg Lv 1 70 pts. 61,450
  7. Avatar for blazegeek 7. blazegeek Lv 1 65 pts. 61,391
  8. Avatar for Sandrix72 8. Sandrix72 Lv 1 60 pts. 61,389
  9. Avatar for AlkiP0Ps 9. AlkiP0Ps Lv 1 56 pts. 61,351
  10. Avatar for grogar7 10. grogar7 Lv 1 52 pts. 61,315

Comments

grogar7 Lv 1

Segment K80? I don't understand this designation. Segment 80 is a glycine. Did you mean segment #8, which is a lysine (K)?

LociOiling Lv 1

I agree that K80 is a mystery. There's no chain K, chains A-J only, so K must mean lysine. But there's a lot of lysine in this puzzle.

Also, the 10 chains in this puzzle are a match for α-synuclein, which gets a lot of entries in the PDB, for example:

https://www.rcsb.org/structure/6CU7

6CU7 looks a lot like our puzzle. The description mentions "fibrils".

I guess this puzzle is a plaque of prions, or something like that.

horowsah Staff Lv 1

Ah- K is indeed for lysine, and 80 is the segment number within each of the stacked fibrils. Each stack member of the stack has the same sequence. Does that now make more sense?

There are actually several similar structures in the PDB as this, many with the same sequence; they fibrils isolated from different patients that have the same protein forming fibrils in their brains.

grogar7 Lv 1

So segment #67 (PDB A80) and its analogs in the other layers of the stack is the one in question. I then echo Bletchley Park's query. What do you think is suspicious about it??

horowsah Staff Lv 1

I didn't really want to bias you as to what we thought might be suspicious to see what you think. But I'll give an outline of my thoughts on it.

It's a lysine, which are notorious for being quite flexible, and therefore the density for the sidechains are often incomplete. The thing that caught my eye is that it looks like that wasn't the assumption when its rotamer for it was chosen. Turns out, it seems like this might make a difference in how people interpret how these fibrils form in disease.