Icon representing a puzzle

2459: Revisiting Puzzle 55: Scorpion Toxin

Closed since almost 2 years ago

Novice Overall Prediction

Summary


Created
May 01, 2024
Expires
Max points
100
Description

This is a throwback puzzle to the early days of Foldit. This scorpion toxin binds to voltage-gated ion channels in insects, resulting in full-body paralysis. The protein contains eight cysteine residues that oxidize to form four disulfide bonds. We are revisiting old Foldit puzzles so we can see how useful the recent additions to the game have been and to provide newer players with problems that are still scientifically relevant.

Sequence
VKDGYIVDDVNCTYFCGRNAYCNEECTKLKGESGYCQWASPYGNACYCYKLPDHVRTKGPGRCH

Top groups


  1. Avatar for Anthropic Dreams 100 pts. 10,739
  2. Avatar for Go Science 2. Go Science 52 pts. 10,728
  3. Avatar for Marvin's bunch 3. Marvin's bunch 24 pts. 10,471
  4. Avatar for Australia 4. Australia 10 pts. 10,418
  5. Avatar for L'Alliance Francophone 5. L'Alliance Francophone 4 pts. 10,339
  6. Avatar for Contenders 6. Contenders 1 pt. 10,288
  7. Avatar for FamilyBarmettler 7. FamilyBarmettler 1 pt. 10,130
  8. Avatar for BOINC@Poland 8. BOINC@Poland 1 pt. 9,350
  9. Avatar for VeFold 9. VeFold 1 pt. 9,293

  1. Avatar for LociOiling
    1. LociOiling Lv 1
    100 pts. 10,738
  2. Avatar for Galaxie 2. Galaxie Lv 1 33 pts. 10,732
  3. Avatar for silent gene 3. silent gene Lv 1 8 pts. 10,725
  4. Avatar for gmn 4. gmn Lv 1 2 pts. 10,711
  5. Avatar for Bruno Kestemont 5. Bruno Kestemont Lv 1 1 pt. 10,364
  6. Avatar for Serca 6. Serca Lv 1 1 pt. 8,826

Comments


Serca Lv 1

It's interesting that this small protein has so many cysteine bridges. It seems that these cys bonds are critical for high its high toxicity: Due to their specific structure stabilized by disulfide bonds, they are able to bind precisely and with high affinity to ion channels on the surface of nerve cells.

Its shape looks pretty much like a beta-type sodium channel toxin (Nav channel activators) discussed in this paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145618/
They call it P15226, which is 1B7D protein in PDB.

"Their specificity is so great that peptides with 96.72% similarity in their residues (or two amino acid substitutions) show a major disparity in interaction, making them lethal and/or responsive at the nanogram level"

I guess that means that if we take out a few cysteines from this protein, there will be no original shape left.