We did this crazy project where we tried to see if proteins could interact with their mirror image ligand. Seems impossible when proteins need to form 3D structures to interact. But what about if the interaction remains disordered??? www.nature.com/articles/s41... - ThreadSky

estellaan.bsky.social • 91 days ago

We did this crazy project where we tried to see if proteins could interact with their mirror image ligand. Seems impossible when proteins need to form 3D structures to interact. But what about if the interaction remains disordered???

https://www.nature.com/articles/s41586-024-08271-6

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estellaan.bsky.social•91 days ago

Turns out, chirality doesn’t matter at all in a completely disordered interaction. What about interactions that are a little bit disordered? Even so, a weaker interaction still occurs. This shocked us because it seems common sense that ANY structure would preclude interaction

estellaan.bsky.social•91 days ago

It seems there is a grey zone in which interactions with some disorder can still occur regardless of chirality. What does this mean for biochemical ancient history? Why did we end up in a world that is strictly made up of left handed proteins when these interactions can occur???

estellaan.bsky.social•91 days ago

I’ve been so thrilled and honoured to be a part of this work alongside Amanda and @bbkrage.bsky.social as well as all of the other authors. And so thankful for funding of course from MSC Actions 🇪🇺

selfdz.bsky.social•91 days ago

📌

jorlab123.bsky.social•91 days ago

Amazing work, well done.

klausenhauser.bsky.social•91 days ago

Very interesting! Just wondering if you’ve tested this with mirror proteins/larger component or solely with mirror peptides. I would presume the same trend (also tons of work for a fully folded mirror protein)

estellaan.bsky.social•91 days ago

No just with the peptides. I think quite hard (or expensive!) to obtain a full protein in D-amino acids, but it would be sooooo cool to do and really a dream experiment especially if it could be 15N labelled too!

klausenhauser.bsky.social•91 days ago

Oh for sure! Just wondering. I have seen papers recently with D-proteins (so I thought they became a bit more accessible) but couple that to isotopic labelling. It sounds like a massive feat

carolynbertozzi.bskyverified.social•91 days ago

Fascinating study!

gomobel.bsky.social•90 days ago

Hi Estella! Could you DM me your email address so I can contact you about this paper? I'm planning an article about it for Chemistry World 🤗

sarahshammas.bsky.social•91 days ago

I've been waiting to see this come out. Congratulations! I look forward to sharing this paper with my undergraduates too :-)

berkleylynch.bsky.social•86 days ago

Fascinating study, thanks. I recall several projects where fully D-amino acid mirror enzymes were chemically synthesized. In these cases the substrates were chiral, and the D-enzymes required mirror image substrates. EG: https://www.cell.com/cell-chemical-biology/pdf/S2451-9456(19)30043-1.pdf

estellaan.bsky.social•86 days ago

Yes that is very cool! I think that nucleotide chirality might be one of the natural pressures leading to our world with predominantly L-proteins. Fun to speculate, hard to test 😅

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