Jason Yu

On a gruelling hunt for rare associated molecules in your #cryoEM particle stack and not sure where to look?

Discover practical tips and tricks in our new case study using #CryoSPARC v4.7.1 where we find and refine a low-population interaction partner!

guide.cryosparc.com/processing-d...

Cryo-EM maps and atomic models of the biotin-containing 3-methylcrotonyl-CoA carboxylase (MCC) complex and long-chain acyl-CoA carboxylase (LCC) complex

New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz

Excited to release BoltzGen which brings SOTA folding performance to binder design! The best part of this project is collaborating with a broad network of leading wetlabs that test BoltzGen at an unprecedented scale, showing success on many novel targets and pushing the model to its limits!

Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator Nature Communications - Here, the authors present the 3.7 Å cryoEM structure of native sodium efflux pump PfATP4 from Plasmodium falciparum, revealing a bound protein that they term...

Learn how our hunt for the native structure of top antimalarial target PfATP4🧂led to the discovery of PfABP, an unknown essential binding partner, out now! @natcomms.nature.com 👉 rdcu.be/eLRlH 🦠🔬❄️

A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria

Figure 1 from the preprint

Check out our preprint! With new molecular mechanisms, 140 subtomogram averages, and ~600 annotated cells under different conditions, we @embl.org were able to describe bacterial populations with in-cell #cryoET. And there’s a surprise at the end 🕵️

www.biorxiv.org/content/10.1...
#teamtomo

Amyloid reconstructions from cryoSPARC

Helical Reconstruction of Amyloids in cryoSPARC?
We present guidelines, limitations & future perspectives for processing amyloids in cryoSPARC @structurabio.bsky.social.
Great collaboration of the Kelly Lab and @landerlab.bsky.social #cryoEM #amyloid www.biorxiv.org/content/10.1...

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

ProteinDJ logo

I am thrilled to release ProteinDJ: a high-performance and modular protein design pipeline. Our open-source workflow incorporates #RFdiffusion, #ProteinMPNN, #FAMPNN, #AlphaFold2 and #Boltz-2. It is a fast, free, and fun way to design proteins (1/5)
doi.org/10.1101/2025.09.24.678028 #proteindesign

Structural basis for mTORC1 activation on the lysosomal membrane - Nature Cryo-electron microscopy was used to study human mechanistic target of rapamycin complex 1 (mTORC1) activation on lysosomal membranes, showing progressive recruitment by RAG–Ragulator, RHEB and R...

Finally in @nature.com 🎉
We uncovered step-wise mTORC1 activation on membrane: RAG–Ragulator recruits, RHEB pushes closer, and direct membrane contacts by RAPTOR + mTOR trigger full kinase activity.👉 The membrane is not just a platform — it’s part of the mechanism.
www.nature.com/articles/s41...

We finally wrote up the paper for LocScale-2.0.

edu.nl/pvhxv

Please try it out. LocScale is evolving & we are actively building in new features and improvements. Your feedback will help us shape the next steps.

Code: cryotud.github.io/locscale/

Work by @alok-bharadwaj.bsky.social and Reinier.

This one is a bit of a departure from the usual and definitely a work in progress!

We found that by using ab initio reconstruction at very high res, in very small steps, we could crack some small structures that had eluded us - e.g. 39kDa iPKAc (EMPIAR-10252), below.

Read on for details... 1/x

🧬 Transcription elongation by RNA polymerase II relies on a web of elongation factors. Our new work shows how IWS1 acts as a modular scaffold to stabilize & stimulate elongation. Fantastic work by Della Syau! www.biorxiv.org/content/10.1...

Structural basis for the dynamic regulation of mTORC1 by amino acids - Nature Using cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for cellular growth.

Nature research paper: Structural basis for the dynamic regulation of mTORC1 by amino acids

go.nature.com/3V8r3Lw

Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug Nature Structural & Molecular Biology - Integrated structural biology approach leveraging in situ cryo-electron tomography reveals molecular details of the native malarial translation...

Our #CryoET story on how a top antimalarial drug candidate perturbs the native malarial translation machinery is out @natsmb.nature.com🥳 rdcu.be/eBbrH

A massive team effort led by @leonieanton.bsky.social Meseret Haile & Wenjing Cheng in collaboration with Jerzy Dziekan & the Alan Cowman! #TeamTomo

YouTube video by Boston Protein Design and Modeling Club BindCraft: one-shot design of functional protein binders

Have no fear if you weren't in the packed audience this week for @martinpacesa.bsky.social's awesome seminar, because you can check out the recording 👇
youtu.be/qQihl6If9vU

Sub-3 Å resolution protein structure determination by single-particle cryo-EM at 100 keV Cryoelectron microscopy (cryo-EM) has transformed structural biology by providing high-resolution insights into biological macromolecules. We report s…

Now out in Structure: Paper on high-resolution #cryoEM using the 100 kV Tundra cryo-TEM by Dimple Karia, Adrian Koh, @abhaykot.bsky.social, @lingboyu.bsky.social, @landerlab.bsky.social and many others. Happy to have contributed to this effort. Check it out:
www.sciencedirect.com/science/arti...

When particles have orientation bias, the resulting maps are often streaked along the missing directions. In this case study, we cover why orientation bias produces anisotropic #cryoEM maps and how you may be able to recover from it!

guide.cryosparc.com/processing-d...

I am pleased to announce Reactor—the complex formation calculator for multi-component protein complex formation experiments. Developed by the Farnung Lab @harvardmed.bsky.social.
reactor-farnunglab.pythonanywhere.com 1/n

Link here! guide.cryosparc.com/processing-d...

Structure, assembly and inhibition of the Toxoplasma gondii respiratory chain supercomplex - Nature Structural & Molecular Biology Here the authors demonstrate that the assembly of mitochondrial respiratory supercomplex (III2–IV) from Toxoplasma gondii is critical for parasite fitness. They reveal the basis for cytochrome b inhib...

Happy to share our latest paper. Result of a great collaboration between @sheinerlab.bsky.social @oninopantsu.bsky.social and Alexander Mühleip’s new group.

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

A) Diagram showing how EtfD transfers electrons from beta oxidation to the menaquinol pool in the membrane, linking beta oxidation to oxidative phosphorylation in mycobacteria. B) A growth curve showing the Mycobacterium smegmatis lacking EtfD can grow when glucose is provided as the carbon source, but has a slight growth delay. Complementing the ∆etfD strain with M. tuberculosis on a plasmid rescues the defect. C) A growth curve showing that ∆etfD M. smegmatis cannot grow on medium where the fatty acid oleic acid is the only carbon source. A plasmid with with M. tuberculosis EtfD rescues the defect.

EtfD links beta oxidation to OxPhos in mycobacteria - recent work suggests that targeting EtfD could shorten #tubeculosis treatment.
But how does EtfD work? And how can you assay its activity?
In his final PhD manuscript @courbongautier.bsky.social provides answers!
www.biorxiv.org/content/10.1...

Mycobacterium tuberculosis partitions the Krebs cycle to persist under iron starvation In this study, we investigated how iron limitation alters central metabolism in Mycobacterium tuberculosis using metabolomics and stable isotope tracing. Our findings reveal a well-orchestrated metabo...

Proud to share the results of a study that tells us how M. tuberculosis remodels central metabolism in response to iron deficiency.
@agnese75.bsky.social @luizcarvalholab.bsky.social
www.biorxiv.org/content/10.1...

Grappling with poorly-resolved ligand binding sites in #cryoEM maps?
Check out our new case study on a peptide ligand-bound GPCR showing how practical tips and features in #CryoSPARC v4.7 improve locally refined map quality and reveal clearer ligand density!
guide.cryosparc.com/processing-d...

Conformational changes in the motor ATPase CpaF facilitate a rotary mechanism of Tad pilus assembly - Nature Communications The bacterial Tad pilus extends and retracts using a single bifunctional ATPase CpaF. Here, the authors employ cryo-EM, fluorescent microscopy, and AlphaFold modelling to propose how a rotary mechanis...

Thrilled to announce my first PhD publication in Nature Comms! We determined structures of the Tad pilus ATPase CpaF from Caulobacter. We use these structures to propose how CpaF employs a rotary mechanism of catalysis to drive Tad pilus assembly.
www.nature.com/articles/s41...

Structure and infection dynamics of mycobacteriophage Bxb1 Mycobacteriophage Bxb1 is a well-characterized virus of Mycobacterium smegmatis with double-stranded DNA and a long, flexible tail. Mycobacteriophages…

Hurray, it is finally out! Meet bacteriophage Bxb1 - the subject of my first full-phage cryo-EM study. My structures are beautifully complemented by the Park Lab’s cryo-ET analysis, shedding light on mycobacteriophage structural changes during infection.

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

Structure of Mycobacterial NDH-2 Bound to a 2-Mercapto-Quinazolinone Inhibitor Mycobacterial type II NADH dehydrogenase (NDH-2) is a promising drug target because of its central role in energy metabolism in Mycobacterium tuberculosis and other pathogens, and because it lacks a k...

Now published J. Med. Chem! @zestytoast.bsky.social's structure of type II NADH dehydrogenase from mycobacteria. A promising drug target for TB & other mycobacterial infections, Yingke demonstrates how an inhibitor can block transfer of electrons from NADH to the ETC.
pubs.acs.org/doi/full/10....

The final version of our work on the in-cell architecture of the mitochondrial respiratory chain is now online in @science.org 🎉
You can find the full story here www.science.org/doi/10.1126/...
@verenaresch.bsky.social did a wonderful job on the cover and animation, she really brought it to life 👩‍🎨

Beautiful art! 🖋️

We've been studying mechanisms of resilience that protect lysosomes from damage and wrote a review on the topic. We consider lysosomal stress and damage on a spectrum. Please help me share as this is my first post 😀 and I don't have many followers! 🙏 Open Access: www.embopress.org/doi/full/10....

Structural biology is in an era of dynamics & assemblies but turning raw experimental data into atomic models at scale remains challenging. @minhuanli.bsky.social and I present ROCKET🚀: an AlphaFold augmentation that integrates crystallographic and cryoEM/ET data with room for more! 1/14.