Dirk H. Siepe
@dhsiepe
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Joined June 2022
AlphaBind paper is out. Trains on 7.5M Ab‑Ag reads + protein LMs to build a 15M engine for rapid affinity boosts🚀 Single round delivers up to 74× tighter binding from just 3‑11 edits, yielding thousands of diverse, developable variants🧬#AntibodyAI #bioAI
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I am happy to share that we have a great opportunity for a postdoctoral scientist. Please share.
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Another great collab with @jjanetzko, @rvshivand, Jonathan, the Kobilka lab and @GreenstoneBio, stay allosterically tuned… https://t.co/5XKV82NoSl
biorxiv.org
Arrestin proteins bind active G protein-coupled receptors (GPCRs) through coordinated protein-protein, protein-phosphate, and protein-lipid interactions to attenuate G protein signaling and promote...
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Setting up a lab has been no joke. Today, I'm stoked to have one more piece of my postdoc work out in the wild. Several more manuscripts to go, and I don't have a lot of time for a tweetorial today, but enjoy and happy to get any feedback on this story. https://t.co/vkbL8m7YFG
biorxiv.org
Arrestin proteins bind active G protein-coupled receptors (GPCRs) through coordinated protein-protein, protein-phosphate, and protein-lipid interactions to attenuate G protein signaling and promote...
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Structural Diversity of Metabotropic Glutamate Receptor/Beta-Arrestin Coupling https://t.co/sa4O6ZNVOH
#biorxiv_biophys
biorxiv.org
Despite the widespread physiological roles of beta-arrestin (β-arr) coupling in G protein-coupled receptor (GPCR) regulation, the molecular basis of GPCR/β-arr interaction has been studied primarily...
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…high jacking the UPS, great read featuring bifunctional and multifunctional degraders: https://t.co/XABfcraF8N
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Excited and proud to have this paper published with @NatureComms today! Great project led by @DrJuanLMendoza at @UChicagoPME and @HHMINEWS. Excited for the future of the field - stay tuned for a full breakdown and walkthrough of our results!
nature.com
Nature Communications - IFNλ4 has posed a conundrum in human immunology, leading to structural and functional questions about the protein. Here, the authors use protein engineering and cryoEM...
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Just before the New Year: BindCraft v1.5! Please fill out this form to request new features and help us make BindCraft even better. https://t.co/J71Y2x5efd
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😀Excited to share our new findings in @CellCellPress! https://t.co/X3nwkEhfjp Dynamic allostery drives autocrine and paracrine TGF-ß signaling #TGFbeta #DynamicAllostery #CryoEM #StructuralBiology #MedicalInnovation
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Such a amazing story, congrats to @vcluca1 and the whole team
I am excited to share our @NatureComms paper describing the structure of #LAG3 bound to MHC-II. This project was carried out by @SuperMQQ et al at @MoffittResearch and provides new insights into the mechanism by which LAG3 suppresses T cell activation.
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What if you could design binders to specific spots/motifs on target proteins: conserved epitopes on pandemic viral phosphoproteins, disordered regions on dysregulated transcription factors, or even breakpoints on fusion oncoproteins? That would unlock unprecedented specificity
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Today we remember and celebrate the life of Bill Weis. Our friend, colleague, & mentor. We scientists are lifelong learners by temperament & necessity. Bill fueled our learning daily. 1/n
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Excited to the see the diversity of and emerging successes for extracellular protein degradation (eTPD) to pair with the established successes of intracellular protein degradation (iTPD). @Kaan_Kumru_ and I are thrilled to share this review! ...no protein is safe!
Check out this new review from our lab on extracellular targeted protein degradation (eTPD). Just came out on Nature Reviews Drug Discovery:
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Extracellular targeted protein degradation: an emerging modality for drug discovery https://t.co/6sD7kFSBkd This new review by @realJimWells & @Kaan_Kumru_ covers systems for extracellular targeted protein degradation, including LYTACs, ATACs, AbTACs, PROTABs and KineTACs
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Want to hunt down the cullin-RING E3 #ubiquitin ligases involved in your favorite pathway or #DegraderDrug? Exited that our story on probing active (neddylated) #CRL E3 complexes using conformation specific probes is out now! https://t.co/n3htWsBLrW
nature.com
Nature Chemical Biology - Henneberg et al. developed conformation-specific antibodies enabling probing NEDD8-activated cullin–RING ubiquitin E3 ligase networks in response to extracellular...
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Congrats to Alex on his Notch paper published in Science Signaling! Special thanks to our fantastic team - Emily, Lena, Drew, Julia and collaborators. Click here to read the paper.
science.org
Proteolytic liberation of the Notch intracellular domain occurs at an intracellular compartment.
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The Human Cell-Surface Interactome Project, deposited by Chris Garcia's lab, is now available https://t.co/JSxY4lbf51
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Excited to share the latest work from my time in the Garcia Lab: Receptor Elimination by E3 Ubiquitin Ligase Recruitment (REULR), a Nanobody based, modular mix & match Targeted Protein Degradation (TPD) toolbox to target cell surface receptors. @ACSSynBio
pubs.acs.org
In recent years, targeted protein degradation (TPD) of plasma membrane proteins by hijacking the ubiquitin proteasome system (UPS) or the lysosomal pathway has emerged as a novel therapeutic avenue...
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@TheCoxLab and @Coon_Labs scientists succeeded in developing a new method to generate a more detailed #proteome than ever before, providing insights into how #GeneticVariants and #SpliceVariants in humans impact the proteome. Published in @NatureBiotech
https://t.co/QZmAEQQRFw
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