PlessLab

Ion channels are drugged routinely, but hitting one subtype and sparing close relatives remains difficult. We designed a de novo miniprotein binder against human ASIC1a, a channel that contributes to turning acidosis into neuronal death during stroke. Preprint: www.biorxiv.org/content/10.6... 1/n

bsky.app/profile/ples...

bioRxiv Biophysics@biorxiv-biophys.bsky.social

A deep learning-generated hASIC1a miniprotein inhibitor confers neuroprotection in stroke https://www.biorxiv.org/content/10.64898/2026.10.04.755611v1

Big thanks to everyone involved, especially project lead @janina-sormann.bsky.social, and our great UCPH collaborators @josephrogers.bsky.social, @henrietteautzen.bsky.social and @Changsi Cai, as well as @naniontech.bsky.social. 6/n

Grateful for funding by @DFF @novo-nordisk.bsky.social @lundbeckfonden.bsky.social #ProteinDesign #DeNovoDesign #IonChannels #Stroke #CryoEM #Electrophysiology #DrugDiscovery

The mechanism turned out to be quite interesting: Denasin1 is disordered in solution and only adopts its designed helix-turn-helix fold upon binding to the channel. As far as we know, this is the first fold-upon-binding de novo miniprotein binder. 4/n

Worth noting and possibly related to the above: Denasin1 would not have passed conventational cut off criteria for promising binders. @janina-sormann.bsky.social had the intuition to include it anyway and found it to outperform all other tested binders. 5/n

We used RFdiffusion, ProteinMPNN, AlphaFold2 filtering, then automated patch clamp as the experimental screen, with no binding assay in between. From ~12,000 backbones and ~70,000 sequences, 76 were expressed and two turned out to be nanomolar inhibitors. 2/n

Denasin1 is a 44 amino acid peptide with an IC50 <50 nM and near-complete block of hASIC1a, but no inhibition of hASIC1b/2a/3. Cryo-EM confirmed the predicted binding mode and in a mouse stroke model it reduced infarct volume by more than 50%. 3/n

@biophysicalsoc.bsky.social

Very excited about every single one of the five abstracts that my group has been involved in that were submitted for the BPS 2027 meeting in Philly! #BPS2027 #biophysics #ionchannels

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Biophysical Society

Have you submitted your abstract yet for #bps2027? The deadline is fast-approaching, on October 1! Don't miss out on the opportunity to share your research at the largest gathering of biophysicists from around the world! buff.ly/VqqKII9

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Alexis Rohou

@alexisrohou.bsky.social

10 Sept

Genentech Structural Biology is hiring a Principal Scientist - please share! We're looking for someone with expertise in solving structures and in computational techniques related to dynamics - MD, ensemble modeling, ensemble docking, and/or related methods.

careers.gene.comPrincipal Scientist, Structural Biology in South San Francisco, California, United States of America | Research & Development at GenentechApply for Principal Scientist, Structural Biology job with Genentech in South San Francisco, California, United States of America. Research & Development at Genentech

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Journal of General Physiology

@jgp.org

3 Sept

Tunable AMPA receptor function via recurrent #evolution of heterotetramers. New study from Yuhong Wang, Alexander Edwards, Jelena Baranovic, and Timothy Lynagh @msarscentre.bsky.social: rupress.org/jgp/article/... #MolecularPharmacology #MembraneTransport #Biochemistry #Biophysics #IonChannels

Voltage-clamp fluorometry turns 30 this year - thank you, Isacoff & Bezanilla! It has been a great tool to watch the outside of channels move, but of less use on the inside. That’s a shame because that is where a lot happens, incl. conformational changes related to sodium channel inactivation. 1/x

This one took patience: many oocytes, lots of peptide, and a lot of persistence - big thanks to @lauriepeverini.bsky.social and the whole team for keeping at it. Gratefully funded by the @lundbeckfonden.bsky.social and the EU's Marie Skłodowska-Curie Actions. 4/x

Preprint: www.biorxiv.org/content/10.6... #IonChannels #ChemicalBiology #Electrophysiology #Nav15 #Biophysics #Preprint

In our new preprint we placed a bright, photostable rhodamine in the intracellular domain of the human Nav1.5, next to the IFM motif, by having a living cell splice in a chemically synthesized 77-mer peptide via two orthogonal split inteins. 2/x

It works and the signal tracks inactivation (both fast and steady-state) rather than activation. And two things binding at distant sites, the auxiliary protein iFGF12A at the C-terminus and lidocaine in the pore, both allosterically tune the kinetics of the DIII–DIV linker movements. 3/x

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Sergey Ovchinnikov

@sokrypton.org

15 Aug

Replying to @sokrypton.org

Try for your protein at py2dmol.solab.org (Style → Cartoon)

nature.comConformational plasticity of human acid-sensing ion channel 1a - Nature Structural & Molecular BiologyUsing cryo-electron microscopy, Cahill, Hartfield et al. identified six structural states of human acid-sensing ion channel 1a, revealing how acidic conditions and peptide toxins regulate channel acti...

Big thanks to Isabelle Baconguis (Vollum Institute) and her group for including us in their epic foray into the structural plasticity of ASICs, now out in Nature Structural and Molecular Biology: www.nature.com/articles/s41... 1/4

We propose for the open state to display linear transmembrane helices, delineate mechanistic differences between proton and toxin activation and show that desensitization involves an unexpected conformational diversity in the transmembrane domain. 3/4

Special thanks to Stephanie Heusser, Nadine Ritter, Mette Homann Poulsen for their efforts on our end. 4/4

Using a combination of cryo-EM, electrophysiology and voltage-clamp fluorometry, we show that ASICs display an unexpected structural diversity, resulting in (at least) 6 major conformations. 2/4

grc.org2026 Ion Channels Conference GRCThe 2026 Gordon Research Conference on Ion Channels will be held in South Hadley, Massachusetts. Apply today to reserve your spot.

12 July

En route to the 2026 ion channel GRC - looking forward to seeing everyone and catching up on everything related to those magic proteins! www.grc.org/ion-channels...

@cryoempapers.bsky.social

8 Apr

One week left to apply for the EMBO/FEBS lecture course on #ionchannels and #transporters in beautiful Erice in May 2026: meetings.embo.org/event/26-ion... Please share

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cryoEM papers

4 Apr

Cryo-EM structures of human P2X2/3 heteromer channel reveal the structural basis of ligand selectivity pubmed.ncbi.nlm.nih.gov/41931608/ #cryoEM

@moalquraishi.bsky.social

15 Mar

Excited to be on my way to the Ligand Recognition and Molecular Gating GRC - many of our present projects started at this meeting 10 (!) years ago! @Nalcn @Split inteins

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Mohammed AlQuraishi

13 Mar

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

6 Mar

3000th clone added to our clone library. Happy weekend

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Cordero-Vásquez Lab

@cvlab.bsky.social

27 Jan

Sudha (@chakrapanilab.bsky.social) and Julio (@cvlab.bsky.social) are organizing the 2026 Ion Channel Gordon Research Conference: Ion Channels Across Scales — Bridging Molecular Events to Physiological Outcomes, to be held at Mount Holyoke College, July 12–17, 2026. 1/3

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Isabel del Pino Lab

@idelpinolab.bsky.social

23 Jan

Kicking off 2026 on a positive note! Check out our latest work on developmental channelopathies. #IonChannels #NALCN #IHPRF1

bioRxiv Neuroscience@biorxiv-neursci.bsky.social

Preferential vulnerability of cortical GABAergic interneurons to Nalcn deficiency https://www.biorxiv.org/content/10.64898/2026.01.21.700772v1

@lorneproteins.bsky.social

16 Jan

Time to sign up! Registration for the joint FEBS/EMBO course on ion channels and transporters in Erice, Italy (May 13-19th 2026) is now open: meetings.embo.org/event/26-ion... Please share and repost.

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Lorne Proteins

14 Jan

Lorne Proteins 2026 🏖️ Leach Lecturer Carol Robinson, Oxford, on establishing mass spec as a viable technique for structure/function studies; and John Kuriyan, Vanderbilt University, on the structural plasticity and evolutionary potential of DNA clamp loaders. 🔗 Register now: www.lorneproteins.org

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eLife

@elife.bsky.social

28 Dec 2025

A new community-driven lab handbook for reducing conflict and creating more positive and equitable work environments gets strong support from a survey of 200 researchers. buff.ly/K7CGFLV

@andrewplested.bsky.social

26 Nov 2025

To all trainees interested in channels and transporters: the joint FEBS/EMBO course will go ahead in Erice, Italy from May 13-19 2026: network.febs.org/posts/new-jo... Further details to come soon. Please share and repost.

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Itai Yanai

@itaiyanai.bsky.social

23 Nov 2025

PhD students and Postdocs: The Night Science Podcast (@nightsciencepod.bsky.social) is producing an episode highlighting young scientists talking about their creative process. DM me if you'd like us to consider you for this, & read below what PhD student Davis Garner will contribute! ⬇️

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Andrew Plested

15 Nov 2025

Game changer, no doubt. Commercial systems will have expensive consumables I suppose, but huge savings to be made in cell culture, and many important but sparse native targets come into play. Crispr-tagged targets from iPSC neurons, for example. TRPC6 blind? 🤯

Janine Brunner@janinebrunner.bsky.social

MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony. Or from a single dish of HEK cell culture in the case of two membrane proteins. Out in Nature Methods now! lnkd.in/gpyBSceg Wonderful collaboration with the Efremov lab.

13 Oct 2025

Very grateful to have been able to attend the second-ever NALCN conference. This provided a fantastic opportunity to catch up with collaborators and meet patients and families affected by NALCN-related diseases. Huge thanks to everyone at the Channeling Hope Foundation for making this event happen!

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Magnus Bauer

@kinasekid.bsky.social

30 Sept 2025

Phosphorylation on tyrosines control key pathways in immunity, cancer, and metabolism. For the first time, we can now design proteins that specifically recognize individual phosphotyrosines, even in disordered regions. (1/8) Preprint: www.biorxiv.org/content/10.1...

29 Sept 2025

When I started working on ion channels 20+ yrs ago, I could have never imagined how many channels there are to explore! Now I’m delighted to be heading to thematic meetings on two of our favorite channels in the span of just weeks - can’t wait to catch up with the ASIC and NALCN communities!

After years in making, I am glad to be able to share our attempt on establishing a framework for combined functional and computational assessment of variant pathogenicity in the sodium leak channel NALCN: www.biorxiv.org/content/10.1...

Collaborator @amelierocks.bsky.social complemented this with predictions of protein stability and conservation scores. In combination with functional work this establishes a framework for classifying suspected disease variants, which we hope will aid assessment of NALCN variant pathogenicity

A huge thank you to everyone involved and of course @lundbeckfonden.bsky.social, @carlsbergfondet.dk and DFF for funding.

De novo and inherited NALCN variants can lead to severe developmental syndromes. Although variants of uncertain significance or presumed pathogenic variants have been studied in heterologous systems before, there is no generally accepted framework on how to assess or predict variant pathogenicity.