Max Stammnitz
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maxstammnitz.bsky.social
Max Stammnitz
@maxstammnitz.bsky.social
Postdoc at @crg.eu Barcelona,
previously PhD at Cambridge University
Genomics | Mutational Scanning | Molecular Evolution 🧬🌱
www.pyrisentinel.eu ⛰️🌊 www.puntseq.com
Congrats @ferriol.bsky.social and co!!
October 9, 2025 at 6:35 PM
... so please have a look at our preprint and get in touch if you’d like to learn more, explore and use the data, etc 🙂

AND: definitely also check out @taylor-mighell.bsky.social's fascinating story on GPCRs – with even more receptor dose-response curves!

www.biorxiv.org/content/10.1...

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The genetic architecture of G-protein coupled receptor signaling
G-protein coupled receptors (GPCRs) are the most abundant class of human receptors and drug targets. The vast majority of GPCR drugs bind the conserved orthosteric pocket, which can lead to non-specif...
www.biorxiv.org
June 2, 2025 at 1:36 PM
Deep mutational scanning is developing really fast. One of the new directions lies in the exploration of larger, more dynamic proteins. Another in the study of small-molecule interactions.

Chemically inducible receptors and other glueable dimerisation systems offer us one way forward …



[6/7]
June 2, 2025 at 1:36 PM
These rich data allow us to fit thousands of dose-response curves.

With these we can systematically compare mutants’ key signalling parameters including basal phosphatase binding, hormone sensitivity and maximum response.

And there are lots of cool examples & correlations, surprises … 🔎🕵️💚

[5/7]
June 2, 2025 at 1:36 PM
Now what does one get out of this??



A massive map of position-, amino acid-, and small-molecule concentration-dependent variant effects!

[4/7]
June 2, 2025 at 1:36 PM
To better understand this ABA receptor’s genetic encoding, we mutated every position to all 20 amino acids.

A glueable protein complementation assay (GluePCA) then allowed us to measure the relative binding strength of each receptor variant vs. phosphatase – at 12 different dosages of ABA.

[3/7]
June 2, 2025 at 1:36 PM
PYR/PYL receptors (grey) are key to plant water homeostasis and stress signalling. 💦🌱🌞

Abscisic acid ('ABA', green), is bound through a deep hydrophobic pocket. This triggers the allosteric closure of two loops which generate a new binding interface with response phosphatases (white).



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June 2, 2025 at 1:36 PM