1462: Reindeer Beta-lactoglobulin

Summary

Name:

Status:

Closed

Created:

12/20/2017

Points:

100

Expired:

01/04/2018 - 23:00

Difficulty:

Intermediate

Description:

This protein is a component of reindeer milk. Beta-lactoglobulin is a protein found in the milk of many mammals, including cows and sheep, but not in humans. Its natural function is still unknown. The structure of this protein was determined (with some difficulty) by x-ray crystallography in 2006. However, parts of the published structure are a little bit problematic. We want to see if Foldit players can fold this protein starting from an extended chain. Secondary structure predictions (from PSIPRED) are marked on the starting structure, and provide clues about where the protein might form helices and sheets! Note that, due to the large size of the protein, this puzzle will be active for two weeks.

Sequence:

IIVTQTMKDLDVQKVAGTWYSLAMAASDISLLDAQSAPLRVYVEELKPTPGGDLEILLQKWENGKCAQKKIIAEKTEIPAVFKIDALNENKVLVLDTDYKKYLLFCMENSAEPEQSLACQCLVRTPEVDDEAMEKFDKALKALPMHIRLSFNPTQLEEQCRV

Categories:

Overall, Prediction

Rank

Group

Score

Points

Gargleblasters

10,183

100

10,055

10,030

9,961

9,899

Rank

Player

Group

Score

Points

Blipperman 28 40

Gargleblasters

10,183

100

10,182

10,182

10,180

10,136

Rank

Player

Group

Score

Points

Enzyme 48 5

Gargleblasters

10,160

100

10,068

10,055

10,019

9,974

I am confused about the disulfide bonus on 1462. There are 5 cysteines, at positions 66, 106, 119, 121, and 160. If two or four of these are involved in disulfide bonds, I would expect those two or four to be strongly conserved, that is, there would be cysteines in those spots in many related proteins, and a related protein that has one of the cysteines in a disulfide pair would almost always have the other as well.

Jpred finds 936 homologous sequences (related proteins) for our protein. Of those, 608 have a cys in position 66 - so that cys is strongly conserved. However, none of the others are conserved at anything like the same rate. At positions 106, 119, and 121, respectively, there are only 54, 30, and 6 related proteins that also have a cys there. None of those positions can be providing the selection pressure on position 66 to remain cysteine. 160 is more promising, with 234 related proteins having a cys there, but that's still not close to 608. This makes me wonder if there is some other molecule that residue 66 commonly forms a disulfide bond with, that provides the selection pressure to keep a cys in that spot. The other common AAs at that spot are K, G, Q, S, and N, suggesting that residue 66 is on the surface where it could interact with some other molecule.

Does this line of reasoning make any sense? Is it possible the disulfide is not within our protein but with some other molecule? Do you have some other reason to believe there is a disulfide within our protein?

Sun, 12/24/2017 - 04:49

Susume 89 316

Offline

Joined: 10/02/2011

Groups: Anthropic Dreams

Disulfide bond?

Sun, 12/24/2017 - 13:33

Hanto 91 257

Joined: 05/10/2008

Groups: None

I've already seen hints of a

I've already seen hints of a disulfide during game play, possibly not the point tho.

Tue, 12/26/2017 - 13:45

dbuske 91 2622

Joined: 09/22/2011

Groups: Beta Folders

experiment

I have made a fold just using the rama utility.
I moved the dots to red and green areas into small groups.
running wiggle here and there.
Dots would move to other colors at times which is fine.
Move dots, wiggle move dots, til finished.
I got perfect rama, but not folded up completely.
I doubt this would fold in the lab, but I wanted to
give it a try.