Craig M. Crews

Overcoming research bias: The untapped potential of biomedically important but understudied proteins www.cell.com/iscienc...

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#proteomics #prot-paper

Wnt Signaling: Exploring the origins of a signaling pathway The 19 Wnt proteins found in humans are part of a larger superfamily of proteins that are also found in Archaea and Bacteria.

Wnt Signalling: Exploring the origins of a signalling pathway

Providing order amongst constant traffic: #LMBResearch from Sean Munro (@cellbiol-mrclmb.bsky.social) with John Briggs (@mpibiochem.bsky.social) reveals how GOLPH3 allows COPI vesicles to distinguish between Golgi residents & ER-bound proteins.
Read more: www2.mrc-lmb.cam.ac.uk/protein-sort...

Mapping cryptic phosphorylation sites in the human proteome | The EMBO Journal www.embopress.org/do...

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#proteomics #prot-paper

Targeted citrullination enables p53 binding to non-canonical sites Indeglia et al. describe a new post-translational modification that alters p53 function.

Targeted citrullination enables p53 binding to non-canonical sites

dos Santos et al. provide novel insights into the molecular underpinnings of islet cell dysfunction in #type1diabetes, highlighting pathways that may be leveraged to preserve residual β-cell function and modulate α-cell activity. 🧪
#PancSky

www.jci.org/articles/vie...

LZTR1's Kelch domains bind RAS GTPases like RIT1, MRAS, KRAS, facilitating ubiquitination and degradation, clarifying RAS isoform selectivity. PMID:40934300, Science 2025, @ScienceMagazine https://doi.org/10.1126/science.adv7088 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

A comprehensive genetic catalog of human double-strand break repair The analysis of DNA sequence outcomes provides molecular insights into double-strand break (DSB) repair mechanisms. Using parallel in-pool profiling of Cas9-induced insertions and deletions (indels) w...

Kickstarting our Bluesky🦋 account with great news!
Our REPAIRome study finally out today in
@science.org
www.science.org/doi/10.1126/...

Beyond Wolbachia—Can a small molecule control insect reproduction? Kaur et al. demonstrate reduced histone acetylation as a key mechanism underpinning Wolbachia’s paternal-effect embryonic lethality trait in Drosophila melanogaster. Recapitulation of this trait by in...

#Wolbachia has puzzled scientists with its power to rewire insect reproduction. What if I tell you that we found one of the keys Wolbachia use to rewire its host AND a small molecule inhibitor uses this key to mimic what this microbe has mastered for millions of years.

www.cell.com/cell-reports...

PROTAC targeted protein degraders: the past is prologue - Nature Reviews Drug Discovery Targeted protein degradation with proteolysis-targeting chimeras (PROTACs) has the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules. This article summarizes the first two decades of PROTAC discovery and discusses key areas for the future of this therapeutic modality, including establishing the target classes for which it is most suitable and extending its application beyond oncology.

Inspiring talk by @craigmcrews.bsky.social at the 5th Virtual #ChemBioTalks. He talked about the power of inducing protein-protein interactions for #DrugDiscovery and the paradigm-shift from occupancy-driven to event-driven pharmacology that this enables. www.nature.com/articles/s41...

Back from the brink: programmed cell revival for regeneration | The EMBO Journal EMBO Press is an editorially independent publishing platform for the development of EMBO scientific publications.

Back from the brink: programmed cell revival for regeneration | The EMBO Journal www.embopress.org/doi/full/10....

De novo design of phospho-tyrosine peptide binders

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De novo design of phospho-tyrosine peptide binders [new]
Designs binders for phosphorylated tyrosine sites on clinically relevant targets using a deep generative framework, enabling modulation of signaling pathways.

Check out this new Roadmap, a fantastic team effort by a consortium of ER researchers. Glad we could provide the space for this synthesis, which came out of discussions at a fruitful meeting, see below:

Protein Domain Designer tool for the generation of publication-ready protein domain diagrams

New week, new tool: Find our Protein Domain Designer tool to generate publication-ready protein domain diagrams here: domaindesigner.farnunglab.com

This Wed, we'll have Dr. Allan Drummond (U Chicago) giving a talk on "Rethinking stress granules" in the Physical Properties of the Cytoplasm series. Join us. More info, visit cytophys.org

RNA and Proteins: Who Bosses Whom?

Despair seems like a reasonable course of action
'Some estimates are that up to 20% of the entire proteome can bind RNA and moreover that about 20% of all known protein complexes have an RNA component in them and you really have to think about how to deal with such large figures.'

This week's very rich selection of articles and #preprints on #proteostasis thanks to @biomednews.bsky.social -- biomed.news/bims-proteo/...

Highlight: Predicting protein-protein interactions in the human proteome www.science.org/doi/10.1126/...

Interesting questions:

Why long-lived proteins exist in metabolically active cellular environments ?

How are these proteins maintained over time ?

Predicting protein-protein interactions in the human proteome www.science.org/doi/...

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#proteomics #prot-paper

Predicting protein-protein interactions in the human proteome Protein-protein interactions (PPI) are essential for biological function. Coevolutionary analysis and deep learning (DL) based protein structure prediction have enabled comprehensive PPI identificatio...

Remarkable new human proteome-wide effort to predict protein-protein interactions using coevolutionary signals and deep learning. From Qian Cong in the Eugene McDermott Center at UT Southwestern.

www.science.org/doi/10.1126/...

RNA-binding proteins pull in chromatin loops - Nature Cell Biology During development as cells exit a pluripotent state, chromatin looping interactions are strengthened, but the mechanism for this is unknown. A study now shows that CTCF–RBP interactions increase upon differentiation of embryonic stem cells to neural stem cells, and that the non-coding RNA Pantr1 collaborates with CTCF and RBPs to contract the genome.

🍰Interested in reading more about the study? Here's the N&Vs article written by Ann Dean.
👉https://rdcu.be/eHUxZ
bit.ly/424Iel9

Expanding Polycyclic Tetramate Macrolactam (PoTeM) Core Structure Diversity by Chemo‐Enzymatic Synthesis and Bioengineering Polycyclic tetramate macrolactams (PoTeMs) derive from ornithine-based lysobacterene A. To expand the PoTeM core structure carbon skeleton by a CH2-unit, a synthetic access to lysobacterene A and an ...

The year started with Sebastian’s paper on the substrate promiscuity of the cyclization enzymes IkaBC. The paper includes chemical synthesis combined with exciting chemo-enzymatic transformations generating a plug-and-play system for PoTeMs. Check it out!
onlinelibrary.wiley.com/doi/10.1002/...

The 5th Virtual @chembiotalks.bsky.social on September 30th are one week away. We have an exciting program including our keynotes Sarah O'Connor (@oconnorlab.bsky.social) and @craigmcrews.bsky.social.

Make sure to register for free: web.cvent.com/event/...
#ChemSky #ChemBio

Thrilled that our work is now finally out in Nature Comms!
rdcu.be/eG3vP

We reveal cryo-EM structures of the MRN complex bound to DNA & TRF2 - showing how DNA breaks are sensed and regulated at telomeres.
Fantastic work by first authors @yilanfan.bsky.social @filizkuybu.bsky.social & Hengjun!

NEW PODCAST: ‘A Question of Science’ with Professor Brian Cox.

In every episode, panels of scientists and experts answer audience questions about some of the biggest issues facing us today.

Listen to the first episode, ‘Can we live forever?’: lnk.to/AQOSAgeingBB

Scientist who uncovered how hidden fat drives diabetes wins major research prize - Novo Nordisk Fonden

Among many highlights today #easd25 @easdnews.bsky.social
The Novo Nordisk Foundation
Prize lecture novonordiskfonden.dk/en/news/scie...

Covalent chemical probes Covalent chemical probes represent powerful tools that can be used for biology discovery, target validation, and as starting points for drug discovery ...

Our collection on “Covalent chemical probes” is now complete, edited by our EBM Andy Wilson, and guest editors Keri Backus, Kim Bonger & Alex Adibekian. Congratulations!
www.nature.com/collections/...

The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy - Signal Transduction and Targeted Therapy Signal Transduction and Targeted Therapy - The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy

Summarizing the functions and physiological & #pathological roles of the Bcl2 family, with insights into strategies for the #TherapeuticTargeting of Bcl2 family members in #cancer & other diseases. #medsky @goetheuni.bsky.social

#STTT #OpenAccess:

When the cell needs to respond to the environment: A chromatin-splicing love affair Alternative splicing allows rapid phenotypic adaptation, but the underlying mechanisms remain unclear. Moreau et al. highlight new findings on the critical role of chromatin modifications and 3D nuclear organization in regulating splicing dynamics. Understanding these chromatin-mediated processes provides insights into how organisms sustainably adapt to environmental challenges for rapid responses.

When the cell needs to respond to the environment: A chromatin-splicing love affair

Cartoon of open questions in the study of vesicular pseudopodia.

In their Perspective article, Nadav Scher and Ori Avinoam revisit the role of vesicular pseudopodia in exocytosis of secretory granules.
journals.biologists.com/jcs/article/...