puzzle picture
1817: Coronavirus ORF6 Prediction
Status: Closed

Summary

Name: 1817: Coronavirus ORF6 Prediction
Status: Closed
Created: 03/26/2020
Points: 100
Expired: 04/02/2020 - 23:00
Difficulty: Intermediate
Description: Refold this coronavirus protein! This protein is encoded in the viral genome of SARS-CoV-2, in a region called ORF6, but the protein's structure is still unknown. Evidence suggests this protein inhibits the natural immune response, helping the virus survive and replicate. If we knew how this protein folds, we might be able to figure out exactly how it inhibits the immune system. The puzzle's starting structure shows SS predictions from PSIPRED, and hints which parts of the protein might fold into helices or sheets. Refold this protein to find high-scoring solutions, which will tell us how this protein is most likely to fold!

Sequence:
MFHLVDFQVTIAEILLIIMRTFKVSIWNLDYIINLIIKNLSKSLTENKYSQLDEEQPMEID
Categories: Overall, Prediction

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Comments

Joined: 05/26/2008
Groups: Hold My Beer
Can you post the psipred

Can you post the psipred prediction? so we can see how it weights its choices please

bkoep's picture
User offline. Last seen 3 hours 57 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
PSIPRED Predictions
Conf: 9630646303999999999985389986999999999998102000242227657998789
Pred: CCCCHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHCCCCCCCCCCCCCCCCCCCCC
  AA: MFHLVDFQVTIAEILLIIMRTFKVSIWNLDYIINLIIKNLSKSLTENKYSQLDEEQPMEID
              10        20        30        40        50        60
Joined: 05/26/2008
Groups: Hold My Beer
Thank You !

Thank You !

jeff101's picture
User offline. Last seen 13 hours 24 min ago. Offline
Joined: 04/20/2012
Groups: Go Science
What do the Conf numbers mean?

In the above PSIPRED Predictions, what do the Conf numbers mean?
Is 0 the lowest confidence and 9 the highest?
Is 1 the lowest confidence and 0 (standing for 10) the highest?

jeff101's picture
User offline. Last seen 13 hours 24 min ago. Offline
Joined: 04/20/2012
Groups: Go Science
What are the HEC probabilities for each segment?
Doesn't PSIPRED give for each segment the
probability that the segment is helix (H),
sheet (E), or loop (coil so C)? I think 
these 3 probabilities should total to 1
for each segment. Doesn't PSIPRED also 
give diagrams with 3 letters of different 
heights for each segment, so some segments 
have large H's but small E's and C's, while 
other segments have large C's but small H's 
and E's? Would someone please post a chart 
with the HEC probabilities or an image with 
the HEC letters given in different sizes?

Thanks!
Serca's picture
User offline. Last seen 11 weeks 1 day ago. Offline
Joined: 02/03/2020
Groups: Go Science
Psipred prediction gives long

Psipred prediction gives long helix just like puzzle start structure.
It seems that this protein is transmembrane, but when you wiggle it enough that helix breaks on two parts. So it is possible that both tails of the protein are on the same side of the cell.

Serca's picture
User offline. Last seen 11 weeks 1 day ago. Offline
Joined: 02/03/2020
Groups: Go Science
Isn't this protein transmembrane?

I found a paper from 2007 that researches the functions of the ORF6 protein from a different SARS strain.
It states that its OFR6 is a membrane protein: "we demonstrate that SARS-COV ORF6 protein is localized to the endoplasmic reticulum (ER)/Golgi membrane in infected cells"

If the 1817 OFR6 protein is transmembrane, that means that exists is in non-aquatic enviroment, so hydrophilics should be buried and orange sidechains of this protein have to be exposed outside. In this case we just cannot get high Foldit score for best solutions, isn't it?

Paper:
Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane.
https://www.ncbi.nlm.nih.gov/pubmed/17596301

bkoep's picture
User offline. Last seen 3 hours 57 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Possibly

Cool! I hadn't seen this work!

Glancing at the paper just now, I don't see terribly strong evidence that ORF6 is itself embedded in the membrane. It does look like ORF6 associates with the ER, but that could also just mean that it binds another molecule at the ER. Also, just looking at the ORF6 sequence, I don't see anything that screams "transmembrane" (like a long stretch of hydrophobics).

That said, I have not studied this particular protein, so I can't claim any authority on this subject—there may be other evidence that ORF6 is membrane-embedded! If it is, you are correct that the default Foldit score is inappropriate for structure prediction. To predict the structure of a membrane-bound protein, we would want to adjust our score function to account for the non-aquatic environment.

Joined: 05/19/2017
Groups: None
Tried a transmembrane fold on-stream

It might not be perfectly hydrophobic, but I did end up with a triple helix solution with two "membrane embedded" helices that I tried my hand at satisfying the polar atoms for. Could always be the case that it links up with another protein and offers quaternary structure to cover the rest.

Joined: 05/09/2008
Groups: None
Nice find!

I ran it on a few transmembrane prediction servers and indeed this looks to be the case:

Residues MFHLVDFQVTIAEILLIIMRTFKVSIWNLDYIINLIIKNL were predicted to be a Transmembrane Helix by PSIPRED's Membrane Helix Prediction.

(I wanted to attach a figure, but drupal is garbage)

jeff101's picture
User offline. Last seen 13 hours 24 min ago. Offline
Joined: 04/20/2012
Groups: Go Science
Will you repost this puzzle scored as a transmembrane protein?

Does this mean that after this puzzle ends, you will
post a new version of it scored like a transmembrane
protein would be scored? If you let us load our
solutions from this puzzle into the reposted version,
we could watch them restructure in their new
environment, which would be interesting.

Joined: 05/26/2008
Groups: Hold My Beer
stupid question...

is psipred capable of predicting pi helices and 310 helices ? if so does it specify this in its output ? or is it simply ptedictin alpha/beta/loop

dfonda's picture
User offline. Last seen 13 weeks 5 days ago. Offline
Joined: 11/08/2011
Groups: None
transmembrane thoughts

@Serca @bkoep @S0ckrates @Susume2
Please correct any errors you see as I'm pretty new to this.

Theorizing: ORF6 suppresses imuno so maybe it's either a friendly key or honeypot for white blood/T-cells?
e.g. either white/T/regular cells see the external part (residues 46-61) as a friendly (key) or immune cells grab it and think "oh we know this one already" (honeypot)

The Helix could be straight if it's bound to other stuff in the membrane not shown in this puzzle
the bottom 4 loops could be the connector to ORF7a/7b which might be perepherial membrane proteins?
residues 46-61 could be the key/honeypot that suppress immune function binding to something?

So I made a transmembrane helix similar to this idea
https://drive.google.com/open?id=1Qp7FkbRTFfRTuRLKJYXCigIc3qiUpPVB
my crummy try at it
https://drive.google.com/open?id=1DeoDZDvWTmLy24esRfv4dnpOGTlPyKOT

reference:
Dark Proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses
Rajanish Giri1*, Taniya Bhardwaj1, Meenakshi Shegane1, Bhuvaneshwari R. Gehi1, Prateek Kumar1, Kundlik Gadhave1

https://drive.google.com/open?id=1kAkU7mC9NNGakBbxkrYWIRrMwSj8TRYt

dfonda's picture
User offline. Last seen 13 weeks 5 days ago. Offline
Joined: 11/08/2011
Groups: None
SARS-CoV-1 vs 2 ORF6

SARS-CoV-2: MFHLVDFQVTIAEIL L IIMRTF KVS IWNLD Y II NLIIKN LSKSL TENKY SQLD EEQP MEID
SARS-CoV : MFHLVDFQVTIAEIL I IIMRTF RIA IWNLD V II SSIVRQ LFKPL TKKNY SELDD EEP MELD YP

I didn't space all the diffs as some seemed like group variants like TENKY vs TKKNY

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