Craig M. Crews
@craigmcrews.bsky.social
📤 4052
📥 5636
📝 53
pinned post!
It's an honor to share this year's Passano Award with Ray Deshaies, Ph.D. for the development of PROTACs, a new therapeutic modality that targets proteins for degradation via co-opting the cellular protein recycling machinery.
about 1 year ago
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Shabaz Lab
about 24 hours ago
Project Hail Mary is very good if you ignore the centrifuge debacle. Worthy successor to The Martian.
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Peter DeWeirdt
3 days ago
Excited to see our work out in Science today! Using machine learning to identify prokaryotic immune systems
www.science.org/doi/10.1126/...
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www.nature.com/articles/s41...
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Navigating condensate micropolarity to enhance small-molecule drug targeting - Nature Chemical Biology
Using computational and experimental methods, Ouyang and Chen et al. reveal a drug design principle that the hydrophobic properties of small-molecule drugs significantly influence their ability to eng...
https://www.nature.com/articles/s41589-025-02017-9?utm_source=nature_etoc&utm_medium=email&utm_campaign=CONR_41589_AWA1_GL_DTEC_054CI_TOC-260401&utm_content=20260401
4 days ago
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https://www.biorxiv.org/content/10.64898/2026.03.17.712509v2
7 days ago
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Surya Nagaraja
8 days ago
A little late to Bluesky but my postdoc work w/
@jbuenrostro.bsky.social
now out in
@nature.com
"Epigenetic memory of colitis promotes tumour growth"
www.nature.com/articles/s41...
We wanted to understand how transient inflammation can create an increase in cancer risk, even after full recovery 🧵
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Epigenetic memory of colitis promotes tumour growth - Nature
Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate...
https://www.nature.com/articles/s41586-026-10258-4
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Nature Metabolism
9 days ago
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Often forgotten but essential: long-chain acyl-CoAs in metabolic control
Nature Metabolism, Published online: 26 March 2026; doi:10.1038/s42255-026-01509-9Although long-chain acyl-CoA esters are essential to virtually every aspect of lipid metabolism, their regulatory and signalling roles remain underappreciated. These molecules deserve far greater attention than they receive, because their spatially restricted formation and tightly regulated abundance endow them with potent and highly specific metabolic cues.
http://dlvr.it/TRkLQy
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Magnus Kjærgaard
10 days ago
Why do intrinsically disordered proteins appear larger than they are in SDS-PAGE? We investigate how sequence properties affect SDS-PAGE mobility using synthetic IDRs. Conclusion: We need to consider both SDS binding and the compaction of protein-SDS complexes.
www.biorxiv.org/content/10.6...
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Cell Reports
11 days ago
CBP-IDRs regulate acetylation and gene expression
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CBP-IDRs regulate acetylation and gene expression
Gelder et al. demonstrate that intrinsically disordered regions (IDRs) with divergent sequence properties maintain a functional balance between positive and negative regulation of CBP condensates. This intramolecular mechanism tunes CBP’s sensitivity to lysine acetylation; its disruption fundamentally alters chromatin binding, histone acetylation, and gene expression.
http://dlvr.it/TRj10y
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Alexis Verger 🧬🧫🧪
10 days ago
Atlas of predicted protein complex structures across kingdoms
www.nature.com/articles/s41...
www.biopredictnavigator.cn
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Atlas of predicted protein complex structures across kingdoms - Nature Communications
Protein complexes are the machinery of life, yet mapping their structures across different species is challenging. This study presents an atlas of 1.1million cross-kingdom structures, revealing 181,67...
https://www.nature.com/articles/s41467-026-70884-4
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Jason Buenrostro
11 days ago
It’s well known that inflammation increases cancer risk, but how? The answer: the epigenome "remembers" inflammation and primes stem cells for cancer. Here is our paper:
nature.com/articles/s41...
And a special shoutout to the lead author
@snaga13.bsky.social
A 🧵
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Epigenetic memory of colitis promotes tumour growth - Nature
Colonic stem cells retain a memory of inflammation following disease resolution and there is a mechanistic link between chronic inflammation and malignancy, suggesting potential strategies to mitigate...
https://nature.com/articles/s41586-026-10258-4
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Marcin J. Suskiewicz
11 days ago
And in yesterday's journal club, we discussed this nice paper on transforming antibodies into intrabodies from
@tim-stasevich.bsky.social
et al. The authors put together a pipeline comprising ProteinMPNN to design a stabler protein sequence for the scaffold while keeping the antigen-binding loops.
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AI-assisted protein design to rapidly convert antibody sequences to intrabodies targeting diverse peptides and histone modifications
AI-powered pipeline converts antibodies into functional intrabodies, enabling live-cell imaging of peptides and histone marks.
https://www.science.org/doi/10.1126/sciadv.adx8352
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Laurenz Rabl
12 days ago
www.cell.com/molecular-ce...
Happy to this published. Congrats to the authors. It affirms many things we also saw in our Ribo-seq data irrespective of model (human cell lines vs C. elegans) and sample prep. Very cool, to finally see data on how NAC acts a cotranslational chaperone.
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NAC promotes co-translational protein folding at the ribosomal tunnel exit
Santos et al. reveal NAC’s co-translational interactome, showing compartment-specific nascent chain interactions in human cells. NAC engages emerging chains at the ribosomal tunnel exit via a ribosome...
https://www.cell.com/molecular-cell/fulltext/S1097-2765(26)00136-X?dgcid=raven_jbs_aip_email
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Andrei Goga
15 days ago
Devastated to learn of the passing of the great cancer pioneer J. Michael Bishop. Mentor and friend, it was only a few weeks ago we celebrated his 90th birthday. He taught us that the seeds of cancer lie within us and spent his career combating cancer. 🧪
@ucsfcancer.bsky.social
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Craig M. Crews
18 days ago
The
@natsmb.nature.com
March issue is out! Though always interested in proteostasis, in 2026 we have published and will continue to do so relevant content. Our editorial
www.nature.com/articles/s41...
recaps why the processes and mechanisms of proteostasis continue to interest us.
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No stasis in proteostasis - Nature Structural & Molecular Biology
In this issue of Nature Structural & Molecular Biology, we focus on all things protein homeostasis, highlighting a variety of processes, from protein quality control in translation to autophagy.
https://www.nature.com/articles/s41594-026-01783-x
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Elzo de Wit lab @ NKI
18 days ago
🧵 CTCF is essential for embryonic development, but why has remained unclear. By combining gastruloids with a temporal degron system, we uncovered a surprising dual function — and it changes how we think about CTCF's role in development. 1/8
www.biorxiv.org/content/10.6...
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A dual role for CTCF in development
CTCF is an essential DNA binding protein whose absence leads to embryonic lethality. CTCF is primarily known for its role in 3D genome organization where its N-terminal domain interacts with cohesin to anchor chromatin loops. How CTCF facilitates proper embryonic development remains unclear, necessitating temporal control to resolve its stage-specific functions. By combining gastruloids, an in vitro model of embryonic development, with a degron system to rapidly deplete CTCF at defined timepoints, we show that early CTCF depletion impairs early gastruloid morphogenesis. Surprisingly, ATAC-seq and time-resolved RNA-seq revealed that differentiation was unaffected. CTCF binding is strongly enriched at promoters of downregulated genes. Re-expression of a CTCF variant with an N-terminal truncation, incapable of looping, was sufficient to rescue the expression of CTCF-promoter bound genes and the defects in morphogenesis. However, extended culture (up to 168 hours) of gastruloids reconstituted with N-terminal truncated CTCF led to their collapse. Our work shows that CTCF has a dual function in early mammalian development: at early stages CTCF regulates developmentally important genes through promoter binding, while at later stages its looping function is required for correct development. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 637587, 865459 Dutch Research Council, https://ror.org/04jsz6e67, 016.161.316, VI.C.222.049 Dutch Cancer Society, https://ror.org/0368jnd28, N/A
https://www.biorxiv.org/content/10.64898/2026.03.17.712290v1
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Bogi
17 days ago
Excited to share our new paper on DNA-native holdup! An updated method to measure DNA–protein binding affinities at high throughput - even for full-length transcription factors.
@teamgogl.bsky.social
#TranscriptionFactors
#GATA1
#ProteinDNA
#Biophysics
#Genomics
#MolecularBiology
#OpenScience
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FEBS Press
Native holdup allows the quantitative determination of affinities between full-length transcription factors and DNA. Mutations in either the protein or the DNA can modulate binding strength, which ca...
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.70483
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Lovorka Stojić
19 days ago
Delighted to share our latest work in
@narjournal.bsky.social
on the importance of (lnc)RNA–protein interactions in cell division, and how we identified RSRC2 as a new RBP involved in splicing and centrosome-associated RNA localisation
academic.oup.com/nar/article/...
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RSRC2 is a novel RNA-binding protein that safeguards mitotic fidelity by interacting with the lncRNA C1QTNF1-AS1
Abstract. Mitotic fidelity requires proper chromosome alignment at the spindle equator, a process known as chromosome congression, mediated by well-establi
https://academic.oup.com/nar/article/54/5/gkag229/8526027?searchresult=1&login=false
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Nature Structural & Molecular Biology
17 days ago
ICYMI: New online: Ribosome-associated quality control and related mechanisms
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Ribosome-associated quality control and related mechanisms
Nature Structural & Molecular Biology, Published online: 17 March 2026; doi:10.1038/s41594-026-01771-1Here the author highlights and summarizes the latest advances in ribosome-associated quality control and related mechanisms.
http://dlvr.it/TRZckr
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PastelBio
17 days ago
Single-molecule peptide sequencing through reverse translation of peptides into DNA
www.nature.com/artic...
---
#proteomics
#prot-paper
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Jeremy Baskin
18 days ago
I've been leading a big project at Methods in Enzymology over the past year or so: editing three back-to-back-to-back volumes of articles describing the latest advances in methods for studying lipids and membranes — thank you to the 50
#lipidtime
luminaries who contributed the 51 chapters! Details 👇
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Center of Medical Biotechnology
17 days ago
Great opportunity to join
@hellerschmiedlab.bsky.social
@unidue.bsky.social
@imprs-lm.bsky.social
add a skeleton here at some point
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Leo Kiss
17 days ago
Exciting E3 action from Schulman and
@bartellab.bsky.social
Labs! Massive congrats to
@jakobfarnung.bsky.social
and
@elenaslo.bsky.social
for their amazing work!
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Jacob Corn
18 days ago
Proper organelle regulation during mitosis is a must, but how do membrane-less condensates like PML bodies behave during cell division? In work led by Eric Aird, we found the balance of speckled proteins SP110 & SP100 to be the key.
doi.org/10.1038/s415...
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Manny I. Fox Morone
18 days ago
Only 2% of your serotonin is in your brain, and I've got questions. Read Elizabeth Hlavinka's feature breaking it all down in
@cenmag.bsky.social
:
cen.acs.org/pharmaceutic...
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Serotonin’s role in mental health is more complex than we thought
Recent research has opened the debate on whether chemical imbalances cause depression, anxiety, and other conditions
https://cen.acs.org/pharmaceuticals/neuroscience/ssris-mental-health-debate/104/web/2026/03?utm_source=Staff&utm_medium=Social&utm_campaign=CEN
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Joe Greener
19 days ago
Interesting article and visualisations. Hopefully one day we can run all-atom simulations of the nuclear pore.
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Martin Steinegger 🇺🇦
20 days ago
AlphaFold database has entered the era of complexes. Together with NVIDIA, DeepMind and EBI, we use ColabFold, OpenFold and MMseqs2-GPU to predict ~31 million complexes (homo & hetro-dimers) resulting in 1.8 million high-quality predictions 📄
research.nvidia.com/labs/dbr/ass...
🌐
alphafold.ebi.ac.uk
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Kieran Didi
19 days ago
📢 We’re launching Proteina-Complexa — and after the Jensen keynote mention, we definitely had to post this thread now ;) Atomistic binder design with generative pretraining + test-time compute, plus large-scale wet-lab validation. Project page:
research.nvidia.com/labs/genair/...
🧵 1/n
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Nature Metabolism
19 days ago
#Throwback
🧪 REVIEW | Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution @anneloftsdu.bsky.social , M Emont, E Rosen et al.
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Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution - Nature Metabolism
In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.
http://dlvr.it/TRY08D
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Trends in Immunology
19 days ago
KLHL6: a proteostatic guardian against T-cell exhaustion
#immunology
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KLHL6: a proteostatic guardian against T-cell exhaustion
Cheng et al.'s recent study identifies the Cullin3-RING E3 ubiquitin ligase complexes (CRL3) adaptor protein Kelch-like protein 6 (KLHL6) as a proteostasis regulator whose downregulation in chronically stimulated T cells leads to the accumulation of thymocyte selection-associated high mobility group box protein and phosphoglycerate mutase family member 5, driving T-cell dysfunction. This work positions T-cell exhaustion as a proteostatic disorder and highlights KLHL6 as a promising target for cancer immunotherapy.
http://dlvr.it/TRY1JC
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EMBL-EBI
20 days ago
You asked, we listened. Millions of AI-predicted protein complex structures are now available in the
#AlphaFold
Database. This spans homodimers from 20 of the most studied species, including humans, as well as the World Health Organization’s priority pathogens list.
www.ebi.ac.uk/about/news/t...
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Beckmann Lab
20 days ago
How are histones acetylated as they emerge from the ribosome? We show that NAA40 cooperates with the NAC complex to enable co-translational acetylation of H2A/H4, revealing NAC as a coordinator of nascent protein modification. Read more about our collaboration with
@kirmizislab.bsky.social
#cryoEM
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NAA40 and NAC cooperate in co-translational histone acetylation in humans
Nature Communications - N-terminal histone acetylation by human NAA40 alters epigenetic signaling and affects gene regulation. Here, the authors combine biochemistry and cryo-EM to unravel the...
https://rdcu.be/e8skh
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Journal of Cell Biology
21 days ago
In this Perspective, North,
@doroteaartscience.bsky.social
, Shoemaker et al. highlight the rapidly expanding role of LC3-interacting regions in autophagy.
rupress.org/jcb/article/...
📕 Part of
#Autophagy
2026 👉
rupress.org/jcb/collecti...
#GRC
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Nikolai Slavov
23 days ago
Src is inverted onto the cell surface in cancer cells. Interesting observation with potentially significant implications: Intracellular N-myristoylated proteins, such as Src, may be topologically inverted onto the cell surface in cancer and targeted.
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Mohammed AlQuraishi
23 days ago
New OpenFold3 preview out! (OF3p2) It closes the gap to AlphaFold3 for most modalities. Most critically, we're releasing everything, including training sets & configs, making OF3p2 the only current AF3-based model that is functionally trainable & reproducible from scratch🧵1/9
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Kate Michie
25 days ago
Nice resource! Thanks for making it open access. Check your protein friends people ( and the accompanying paper in Nat. Methods). 🤩🧶🧬
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Chris Lord and Andrew Tutt’s Lab Institute of Cancer Research
25 days ago
We show that normally germline‑restricted HORMAD1 induces aneuploidy in TNBC by disrupting Aurora B/INCENP and weakening spindle assembly checkpoint. This creates sensitivity to MPS1, Aurora B, and BUB1 inhibitors. Work
@icr.ac.uk
funded by
@breastcancernow.bsky.social
and published
rdcu.be/e7Som
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Tumour specific HORMAD1 expression perturbs mitotic arrest and drives sensitivity to mitotic kinase inhibitors
Nature Communications - HORMAD1 expression is typically restricted to germline cells where it has an important role in meiotic recombination but has been shown to be upregulated in triple negative...
https://rdcu.be/e7Som
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Izidor Sosič
26 days ago
Allosteric PROTACs: Expanding the Horizon of Targeted Protein Degradation | Journal of the American Chemical Society
pubs.acs.org/doi/10.1021/...
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Allosteric PROTACs: Expanding the Horizon of Targeted Protein Degradation
Proteolysis-targeting chimeras (PROTACs) have transformed the concept of chemical intervention in biological systems by co-opting the ubiquitin–proteasome system to selectively degrade proteins. A key...
https://pubs.acs.org/doi/10.1021/jacs.5c14840
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Hellerschmied Lab
28 days ago
Check out the highlight! Great work by our lab neighbours
@hemmo-lab.bsky.social
@unidue-zmb.bsky.social
@unidue.bsky.social
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Craig M. Crews
Nature Structural & Molecular Biology
29 days ago
ICYMI: New online: A proteome-wide dependency map of protein interaction motifs
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A proteome-wide dependency map of protein interaction motifs
Nature Structural & Molecular Biology, Published online: 06 March 2026; doi:10.1038/s41594-026-01762-2Ambjørn and Meeusen et al. functionally characterize all reported and a comprehensive set of predicted short linear motifs (SLiMs) using base-editing screens, identifying 450 reported and 264 predicted SLiMs required for normal cell proliferation.
http://dlvr.it/TRM8M3
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Nature Structural & Molecular Biology
29 days ago
ICYMI: New online: A SLiM view of the human proteome
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A SLiM view of the human proteome
Nature Structural & Molecular Biology, Published online: 06 March 2026; doi:10.1038/s41594-026-01770-2Many protein–protein interactions are mediated by compact amino acid stretches known as short linear motifs (SLiMs) that lack a stable tertiary structure. A study now uses high-throughput precision genome editing to decode the function of over 7,000 SLiMs across the human proteome, providing insights into their roles in cellular homeostasis.
http://dlvr.it/TRM8Mk
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Quantitative Degradation Rate Assessment of bioPROTACs Based on Peptide Degrons, E3 Domains, Adapters and Conjugated Small Molecules
Protein-based bispecific degraders, known as bioPROTACs, have emerged as powerful tools for targeted protein degradation through the ubiquitin-proteasome system (UPS). However, the relative efficacy of various recruitment domains within these degraders remains poorly understood. To address this knowledge gap, we conducted a comprehensive comparison of recruitment domains in bioPROTACs, utilizing eGFP as a proof-of-principle degradation target and an eGFP-binding DARPin with known structure as an adapter. Our innovative approach combined microinjection and live-cell microscopy, enabling a detailed assessment of directly measured degradation rates as a single-cell kinetic readout, unaffected by uptake or biosynthesis rates of the degrader, and across the different chemical classes. We examined nine degron peptides, three E3 ligase domains or adapters, and two series of small-molecule binders, linked in various geometries. Our results revealed that bioPROTACs based on E3 or adapter protein domains and small molecules generally exhibited the highest degradation rates, while most degron peptides showed comparatively low efficacy. Notably, for VHL-ligand-1 and thalidomide, the placement of the coupling site and linker position significantly influenced performance. This study provides crucial insights into the design and optimization of bioPROTACs, paving the way for the development of more effective degraders for specific applications. Our findings contribute to the growing field of targeted protein degradation and offer valuable guidance for researchers seeking to enhance the efficacy of bioPROTAC-based therapeutic approaches.
https://pubs.acs.org/doi/10.1021/acschembio.5c00569
about 1 month ago
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Degrons and degradation signals beyond short linear motifs - Nature Chemical Biology
Degrons are degradation signals in target proteins to direct recognition and degradation by the ubiquitin–proteasome system. Wang et al. introduce degrons of different types, with an emphasis on high-...
https://www.nature.com/articles/s41589-025-02056-2?utm_source=nature_etoc&utm_medium=email&utm_campaign=CONR_41589_AWA1_GL_DTEC_054CI_TOC-260302&utm_content=20260302
about 1 month ago
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Terraforming the KRAS lipid landscape - Nature Chemical Biology
ELOVL6 is an acyltransferase involved in the synthesis of saturated and monounsaturated fatty acids. New work finds that inhibition of ELOVL6 function results in mislocalization of oncogenic KRAS from...
https://www.nature.com/articles/s41589-025-01992-3?utm_source=nature_etoc&utm_medium=email&utm_campaign=CONR_41589_AWA1_GL_DTEC_054CI_TOC-260302&utm_content=20260302
about 1 month ago
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Intrinsically disordered domains expand the CAR T cell toolbox - Nature Chemical Biology
A study establishes intrinsically disordered regions (IDRs) as a new module in chimeric antigen receptor (CAR) engineering. The intrinsic biophysics of IDRs — transient, multivalent interactions — can...
https://www.nature.com/articles/s41589-025-02060-6?utm_source=nature_etoc&utm_medium=email&utm_campaign=CONR_41589_AWA1_GL_DTEC_054CI_TOC-260302&utm_content=20260302
about 1 month ago
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Craig M. Crews
Ian Kelsall
about 1 month ago
🚨⚠️ New Preprint Alert! ⚠️ 🚨
www.biorxiv.org/content/10.6...
Screening p97 cofactors,
@prithadg.bsky.social
identified FAF2 as the strongest activator of the p97-UFD1-NPL4 complex. Leveraging her mechanistic descoveries, we designed 𝘥𝘦 𝘯𝘰𝘷𝘰 binders that could also enhance p97 substrate unfolding.
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Craig M. Crews
Signal Transduction and Targeted Therapy
about 1 month ago
An overview of
#LipidMetabolism
in
#Homeostasis
& disease, highlighting how lipid signaling reprograms
#ImmuneCells
and exploring innovative therapeutic strategies for
#Cancer
,
#CardiovascularDisease
, and metabolic disorders.
#OpenAccess
:
doi.org/10.1038/s413...
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Craig M. Crews
Shicheng Guo
about 1 month ago
Check out Nature Chem Biology's latest: De novo protein design crafts potent CRISPR-Cas13 inhibitors. Game-changer for gene editing! PMID:41588195, Nat Chem Biol 2026, @nchembio @OTSociety @NAR_Open
https://doi.org/10.1038/s41589-025-02136-3
#Medsky
#Pharmsky
#RNA
#ASHG
#ESHG
🧪
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De novo design of potent CRISPR–Cas13 inhibitors | Nature Chemical Biology
CRISPR–Cas systems are transformative tools for gene editing that can be tuned or controlled by anti-CRISPRs (Acrs)—phage-derived inhibitors that regulate CRISPR–Cas activity. However, Acrs that can inhibit biotechnologically relevant CRISPR systems are relatively rare and challenging to discover. To overcome this limitation, we describe a highly successful and rapid approach that leverages de novo protein design to develop new-to-nature proteins for controlling CRISPR–Cas activity. Here, using Leptotrichia buccalis CRISPR–Cas13a as a representative example, we demonstrate that Acrs designed using artificial intelligence (AIcrs) are capable of highly potent and specific inhibition of CRISPR–Cas13a nuclease activity. We present a comprehensive workflow for design validation and demonstrate AIcr functionality in controlling CRISPR–Cas13 activity in bacterial and human cells. The ability to design bespoke inhibitors of Cas effectors will contribute to the ongoing development of CRISPR–Cas
https://doi.org/10.1038/s41589-025-02136-3
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Kevin K. Yang 楊凱筌
about 1 month ago
We made FLIP2, a protein fitness benchmark spanning seven new datasets, including enzymes, protein-protein interactions, and light-sensitive proteins, as well as splits that measure generalization relevant to real-world protein engineering campaigns.
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Rune Busk Damgaard
about 1 month ago
This project started with confusion 🤔
www.nature.com/articles/s41...
Loss of LUBAC or OTULIN causes severe inflammatory disease. But patients also show clear metabolic defects. Neither LUBAC nor OTULIN had been linked to metabolic regulation. So where do these metabolic manifestations come from?
add a skeleton here at some point
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Nature
about 1 month ago
Exercise prevents brain ageing and memory loss by strengthening the blood–brain barrier
go.nature.com/4kVU2hy
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How an exercise-activated enzyme helps to keep the brain young
A protein reinforces the blood–brain barrier, which becomes leaky with age.
https://go.nature.com/4kVU2hy
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