A structural code for assembly specificity in GID/CTLH-type E3 ligases Structural characterization of the CTLH-CRA domain-mediated pairing in the CTLH ubiquitin ligase complex enables rational engineering of interfaces with altered binding specificity.

A structural code for assembly specificity in GID/CTLH-type E3 ligases

buff.ly/iC4Ms9u?utm_...

Structure of zebrafish NLRP3 reveals a novel mode of inflammasome activation www.biorxiv.org/content/10.64898/2026.04...

The CASP experiment is about to start - and is still short on challenging prediction targets. Ligand complexes, RNA, …

Closing the loop: Experimentally validated methods in artificial intelligence–driven protein design Artificial intelligence (AI) has reshaped protein design by enabling models trained on large-scale sequence and structure data to generate proteins wi…

[Review] Closing the loop: Experimentally validated methods in artificial intelligence–driven protein design by @kosonocky.bsky.social @sarahalamdari.bsky.social @kevinkaichuang.bsky.social & @avapamini.bsky.social

www.sciencedirect.com/science/arti...

Glycobiology: How enzymes make the right choice during biosynthesis The biosynthesis of an important biopolymer called hyaluronan requires an enzyme that discriminates between two different substrates.

How enzymes make the right choice during biosynthesis

Full-Length Molecular Models of Brain-Derived α-Synuclein Fibrils Reveal a Fuzzy-Coat-Mediated Mechanism for Selective Peptide Binding www.biorxiv.org/content/10.64898/2026.04.16.718707v1 #cryoEM

Our #UExM efforts with @gautamdey.bsky.social & @moorefound.bsky.social featured in @nature.com this month.

Beyond the #science, every image is a thing of beauty.

I think a world-tour exhibition has to happen at one point.

#Expansion #Microscopy

cryoAgent: An agentic workflow for robust and adaptive end-to-end cryo-EM image processing www.biorxiv.org/content/10.64898/2026.04.16.718662v1 #cryoEM

Lecture 2 on data collection TODAY!

Molecular basis of cooperative assembly of the Ndc80-Ska kinetochore complex on microtubules www.biorxiv.org/content/10.64898/2026.04...

CSSB’s first flagship project “PLASMOFRACTION” has successfully deciphered membrane protein complexes in the malaria parasite Plasmodium falciparum.

Find out more: t1p.de/wthx2

@jankosinski.bsky.social, @embl.org, @uni-hamburg.de, @unituebingen.bsky.social, @fmp-berlin.de

Full-Length Molecular Models of Brain-Derived α-Synuclein Fibrils Reveal a Fuzzy-Coat-Mediated Mechanism for Selective Peptide Binding www.biorxiv.org/content/10.64898/2026.04...

New preprint in which we built and simulated full-length models of α-Synuclein fibrils to reveal how the fuzzy coat mediates selective binding of peptides to amyloid fibrils

Work led by Carlos Pintado-Grima in a nice collaboration with Salvador Ventura's lab

doi.org/10.64898/202...

Save your spot! Registration open until May 5th for the CNIO Caixaresearch Frontiers Meeting on metabolism and cancer #CFM_MetCanc

📅 20-22 May 2026

📍Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid

✍️Further information and registration bit.ly/45jaORu 👇

Sephin1 rewires proteostasis through actin-dependent signaling www.biorxiv.org/content/10.64898/2026.04...

Ribosome biogenesis bottlenecks reveal vulnerabilities in cancer www.biorxiv.org/content/10.64898/2026.04...

Seeding patient-derived tau induces tauopathy-specific aggregation and lysosomal disruption in human cells www.biorxiv.org/content/10.64898/2026.04...

Design principles of human membrane protein topology www.biorxiv.org/content/10.64898/2026.04...

Organelle partitioning in the multi-budding yeast Aureobasidium pullulans www.biorxiv.org/content/10.64898/2026.04...

See the intricate worlds of parasites and algae — March’s best science images The month’s sharpest science shots, selected by Nature’s photo team.

Our ExM Atlas of eukaryotes is moving along with more and more images coming in - some featured in nature last month!
Culture we’re provided by @ccapoban.bsky.social & Julius Lukeš during visits last year

www.nature.com/immersive/d4...

🔬 From our April issue (rupress.org/jcb/issue/22...): a 3D super-resolution image of a triple-negative #BreastCancer cell taken with a new optical imaging tool, Landscape Expansion Microscopy (land-ExM). See new method developed by Zhuang, @xyshi.bsky.social et al.: rupress.org/jcb/article/...

ChimeraX-CliX now saves up to 10,000 lines of command history, and you can quickly reverse-search commands with Ctrl+R!
cxtoolshed.rbvi.ucsf.edu/apps/chimera...

The molecular glue CLEO4-88 inhibits the ACAA1 thiolase by induced binding to GID4 - Nature Chemical Biology A small molecule, CLEO4-88, was identified that acts as a molecular glue, linking the E3 ligase subunit GID4 with ACAA1. Instead of triggering ACAA1 degradation, the compound inhibits its enzymatic ac...

A molecular glue CLEO4-88 binds to E3 ligase subunit GID4 to induce a conformational change conducive to binding ACAA1 and inhibiting ACAA1 enzymatic activity instead of triggering ACAA1 degradation

www.nature.com/articles/s41...

Safety considerations for cereblon-recruiting targeted protein degraders Nature Reviews Drug Discovery - Targeted protein degraders that recruit the E3 ligase CRBN are showing promise for challenging drug targets but can have unintended consequences on cellular...

Safety considerations for cereblon-recruiting targeted protein degraders
rdcu.be/feDVy
www.nature.com/articles/s41...

Degradation of unintended neosubstrates of cereblon is a key safety concern for PROTACs and molecular glues. This new Perspective discusses how to approach it

Cell Cycle Control of Nuclear Metabolism Couples Phosphatidylinositol Signaling to Histone Methylation Nuclear metabolism oscillates during cell cycle progression. Quantitative chromatome proteomics and imaging reveal phase-specific dynamics of PIP5K1A and nuclear PIP2, linking phosphatidylinositol me...

🚨 New paper out!
We show that nuclear metabolism is NOT static, it oscillates with the cell cycle.
🔗 advanced.onlinelibrary.wiley.com/doi/10.1002/...
#epigenetics #metabolism #cellcycle #chromatin

The Small-Angle Scattering Biological Data Bank (SASBDB; www.sasbdb.org) has recently passed 5000 deposited data sets, marking a significant milestone for the field @ActaCrystD @IUCr #SmallAngleScattering #BiologicalDataBanks #OpenData doi.org/10.1107/S205...

Brilliant talk from @kashishsingh.bsky.social at Dynamic Cell VI highlighting their work examining cytoplasmic lattices in embryos using cryo-ET. We highlighted this work in our recent preprint list.
Preprint: www.biorxiv.org/content/10.6...
Preprint list: focalplane.biologists.com/2026/04/17/m...

Pharmacological strategies targeting chaperone-mediated autophagy Chaperone-mediated autophagy (CMA) is a selective lysosomal protein degradation pathway that regulates proteostasis, metabolism, and stress adaptation. Genetic- and disease-model studies show that altered CMA activity contributes to diverse human disorders, including neurodegenerative, metabolic, inflammatory, and malignant diseases. However, pharmacological targeting has remained challenging due to a limited understanding of its regulatory architecture and a lack of criteria to distinguish pathway-selective from indirect modulation. Recent advances in mapping CMA regulatory checkpoints and the in vivo validation of CMA-biased compounds have revealed discrete, mechanistically defined control nodes that render CMA pharmacologically tractable. In this review, we synthesize these advances and introduce a mechanistic classification of CMA-modulating compounds by level of action, distinguishing physiological inducers, permissive potentiators, and proximal activators to clarify pathway selectivity and guide translational drug discovery.

Pharmacological strategies targeting chaperone-mediated autophagy

SIB1‐SEC23A undergo ER to chloroplast relocalization to mediate immunity in Arabidopsis thaliana SEC23A mediates membrane trafficking between the endoplasmic reticulum (ER) and Golgi apparatus and interacts with the immunity protein SIGMA FACTOR-BINDING PROTEIN1 in Arabidopsis. Under stress, bot...

In this #OpenAccess report, Peng et al. characterize #Arabidopsis SEC23A, a COPII complex component that mediates membrane trafficking b/t the ER and the #Golgi, as a novel interactor of SIGMA FACTOR-BINDING PROTEIN 1 (SIB1).
doi.org/10.1111/jipb...
@wileylifesci.bsky.social
#PlantScience

Identification of an allosteric site on the E3 ligase adapter cereblon | Nature Cereblon (CRBN) is the target of thalidomide derivatives1 that achieve therapeutic efficacy against some haematologic neoplasias2–4 by recruiting neosubstrates for degradation5–7. Despite the intense investigation of orthosteric thalidomide derivatives, little is known about alternate binding sites on CRBN. Here we report an evolutionarily conserved cryptic allosteric binding site on CRBN. Small-molecule SB-405483 binds the allosteric site to cooperatively enhance the binding of orthosteric ligands and alter their neosubstrate degradation profiles. A survey of over 100 orthosteric ligands and their degradation targets reveals trends in the classes of compounds and neosubstrates in which degradation outcomes are enhanced or inhibited by SB-405483. Structural investigations provide a mechanistic basis for the effects of the allosteric ligand by shifting the conformational distribution of CRBNopen to a novel CRBNint and increasing the CRBNclosed state. The discovery of a cryptic allosteri

Discovery: Cereblon has a conserved allosteric site. SB-405483 binds there, boosting function. Key for new therapeutic strategies beyond thalidomide derivatives. PMID:41565821, Nature 2026, @Nature https://doi.org/10.1038/s41586-025-09994-w #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪