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sobolevsky.bsky.social

@sobolevsky.bsky.social
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sobolevsky.bsky.social @sobolevsky.bsky.social · 10/09/2026
AMPA receptor gating proceeds through an intermediate pre-active state that has structurally remained an enigma. We used cryo-EM as well as full and partial agonists to resolve this state and for the first time structurally reveal the complete gating pathway of AMPARs. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 09/09/2026
Happy to share molecular mechanics of AMPA-subtype ionotropic glutamate receptor (iGluR) pre-activation and complete gating pathway revealed by time-resolved cryo-EM with the help of full and partial agonists. www.nature.com/articles/s41... youtu.be/Uc0Bo2N9puU
youtu.be
Complete gating, including pre-activation, of AMPA-subtype iGluR – Sobolevsky Lab
YouTube video by Sobolevsky Lab
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sobolevsky.bsky.social @sobolevsky.bsky.social · 09/09/2026
AMPA receptor gating proceeds through an intermediate pre-active state that has structurally remained an enigma. We used cryo-EM as well as full and partial agonists to resolve this state and for the first time structurally reveal the complete gating pathway of AMPARs. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 03/09/2026
Happy to share the results of our study of structural and functional regulation of GluA2 AMPA receptor by inhibitory auxiliary subunits GSG1L and TARP gamma5 and by epilepsy-associated disease mutations. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 01/09/2026
Here is a highlight of our work on TRPV1 agonist MSP20, which binds to the vanilloid site, desensitizes TRPV1, and shows the potential of a long-lasting analgesic with neuroprotective effects. cryosparc.com/blog/trpv1-m...
cryosparc.com
The Pain Paradox: Activating TRPV1 to Silence Its Response | CryoSPARC
Combining rational drug design, functional studies, and cryo-EM, researchers characterize a selective TRPV1 agonist that promotes desensitization and prolonged pain relief.
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sobolevsky.bsky.social @sobolevsky.bsky.social · 14/08/2026
Officially published! A new TRPV1 agonist MSP20, which binds to the vanilloid site and desensitizes TRPV1. Our structural and preclinical studies highlight the potential of MSP20 as a long-lasting analgesic with neuroprotective effects. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 05/08/2026
Officially published! Structures of TRPV3 with Olmsted syndrome mutations, which reduce channel’s temperature sensitivity, uncover the molecular basis of this severe genodermatosis and highlight unique features of TRPV3 channel gating. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 05/08/2026
Officially published! Structurally characterized five Olmsted syndrome mutants, which have reduced temperature sensitivity and destabilized non-conducting states, highlighting unique features of TRPV3 channel gating and guiding new therapeutic strategies. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 06/07/2026
Happy to report a new TRPV1 agonist MSP20, which binds to the vanilloid site, desensitizes TRPV1 and suppresses pain signaling for extended time. Our structural and preclinical studies highlight MSP20 as a potential long-lasting analgesic with neuroprotective effects. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 23/06/2026
We used cryo-EM to characterize five TRPV3 mutants causing severe genodermatosis Olmsted syndrome (OS). Our results highlight conserved TRP channel gating mechanisms, uncover the molecular basis of OS and provide a guide for future therapeutic strategies. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 22/06/2026
Mutations in TRP channel TRPV3 cause severe genodermatosis called Olmsted syndrome (OS). We used cryo-EM to characterize five OS mutants, which exhibit reduced temperature sensitivity and disrupt structural elements stabilizing non-conducting states of TRPV3. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 02/06/2026
Mechanism of human TRP channel TRPV6 block by polyamine spermine (SPM). The main binding site of SPM is in the selectivity filter of TRPV6. Amazing collaboration with Chubanov and Efremov labs. www.nature.com/articles/s41...
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Furukawa Lab @CSHL @lab-furukawa.bsky.social · 29/05/2026
As of May 28, this article has been made open access. I apologize for any inconvenience caused earlier. I was uncertain at the time of publication whether I could cover the open access fee. www.nature.com/articles/s41...
nature.com
Mechanism of conductance control and neurosteroid binding in NMDA receptors - Nature
Ion-channel conductance levels are controlled by the bending patterns of pore-forming transmembrane helices in the heterotetrameric neuronal channel GluN1a-2B N-methyl-D-aspartate receptor.
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sobolevsky.bsky.social @sobolevsky.bsky.social · 28/05/2026
Happy to share the stepwise mechanism of human TRP channel TRPV6 block by polyamine spermine. Intracellular spermine makes two transient stops in the channel pore before binding to the main site in the selectivity filter. Collaboration with Chubanov and Efremov groups. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 27/05/2026
Happy to share the stepwise mechanism of human TRP channel TRPV6 block by polyamine spermine. Intracellular spermine makes two transient stops in the channel pore before binding to the main site in the selectivity filter. Collaboration with Chubanov and Efremov groups. www.nature.com/articles/s41...
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CJ Fogler @cjzero.bsky.social · 22/05/2026
The KHL's Gagarin Cup is apparently pretty heavy, Lokomotiv G Alexei Melnichuk needed a spotter here 😂
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sobolevsky.bsky.social @sobolevsky.bsky.social · 11/05/2026
Officially out in Nature Communications: Auxiliary subunits reshape heterotetrameric GluA1/A2 AMPA receptor core! Structures of the most abundant AMPA receptor di-heteromer in the brain GluA1/A2 in the closed, open, and desensitized states! www.nature.com/articles/s41...
nature.com
Auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric GluA1/A2 AMPA receptor core - Nature Communications
Native AMPA receptors are heteromeric complexes of GluA1-4 and auxiliary subunits. Here, authors report structures of the most abundant GluA1/A2 core in the closed, open, and desensitized states, allo...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 08/05/2026
Officially out in Nature Communications: Auxiliary subunits reshape heterotetrameric GluA1/A2 AMPA receptor core! Structures of the most abundant AMPA receptor di-heteromer in the brain GluA1/A2 in the closed, open, and desensitized states! www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 28/03/2026
Hot out of the press: Auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric GluA1/A2 AMPA receptor core! Structures of the most abundant AMPA receptor di-heteromer GluA1/A2 in the closed, open, and desensitized states! www.nature.com/articles/s41...
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John Rubinstein @johnrubinstein.bsky.social · 06/03/2026
I've written a review on what I think is an extremely exciting direction in cryo-EM: Cryo-EM of endogenous membrane proteins in their native lipid bilayer Open access in Quarterly Reviews of Biophysics: doi.org/10.1017/S003...
Figure 1. Cryo-EM of abundant protein complexes in native membranes.Figure 2. Cryo-EM of membrane proteins in vesicles.Figure 3. 3D reconstruction of V-ATPase in native synaptic vesicle membranes.Figure 4. Generation of membrane vesicles for structure determination of proteins in their native lipid bilayer.
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sobolevsky.bsky.social @sobolevsky.bsky.social · 06/03/2026
Claudin 24—A novel enhancer of AMPA receptor fidelity | Science Advances www.science.org/doi/10.1126/...
science.org
Claudin 24—A novel enhancer of AMPA receptor fidelity
The claudin subfamily family member Cldn24 is identified as an AMPAR auxiliary subunit.
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sobolevsky.bsky.social @sobolevsky.bsky.social · 04/12/2025
Happy to share new review of endothelium glutamate receptors in brain pathology. www.frontiersin.org/journals/pha...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 28/11/2025
Oligonucleotide (ON) RGLS4326 designed for treatment of ADPKD caused CNS-related toxicity due to competitive antagonism of AMPA receptors. Understanding this allowed making a new ON devoid of toxicity. Collaboration with Regulus/Novartis! @LauraYen42 @MariaKarela3 www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 28/11/2025
Discovery of new AMPA receptor regulators – RNA molecules that act as competitive antagonists causing CNS-related toxicity when intended for treatment of autosomal dominant polycystic kidney disease (ADPKD). Collaboration with Regulus Therapeutic/Novartis! www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 28/11/2025
Oligonucleotide (ON) RGLS4326 designed for treatment of ADPKD caused CNS-related toxicity due to competitive antagonism of AMPA receptors. Understanding this allowed making a new ON devoid of toxicity. Collaboration with Regulus/Novartis! @LauraYen42 @MariaKarela3 www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 19/11/2025
Now in the journal issue! Structures of kainate receptor GluK2 in the closed apo state and open conducting state bound to agonist kainate and positive allosteric modulator BPAM. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 18/11/2025
Now in the journal issue! Molecular mechanism of activation of kainate receptor GluK2 in complex with auxiliary subunit Neto2. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 06/11/2025
Magnesium site in human oncochannel TRPV6 is formed by two negatively charged residues that are close together in the closed state and separated in the open state. Mg2+ binding keeps these residues together and stabilizes the closed state. With Chubanov/Efremov labs! www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 06/11/2025
Magnesium site in TRPV6 is formed by two negatively charged residues that are close together in the closed state and separated in the open. Magnesium binding keeps them together and stabilizes the closed state. Amazing collaboration with Chubanov and Efremov groups. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 06/11/2025
Magnesium site in TRPV6 is formed by two negatively charged residues that are close together in the closed state and separated in the open. Magnesium binding keeps them together and stabilizes the closed state. Amazing collaboration with Chubanov and Efremov groups. www.nature.com/articles/s41...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 06/11/2025
Happy to share the locking mechanism of human oncochannel TRPV6 inhibition by intracellular magnesium. Amazing collaboration with Chubanov and Efremov groups. www.nature.com/articles/s41...
Magnesium site is formed by two negatively charged residues that are close together in the closed state and separated in the open state. Magnesium binding keeps these residues together and stabilizes the closed state.
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sobolevsky.bsky.social @sobolevsky.bsky.social · 24/10/2025
www.nature.com/articles/s41...
nature.com
Structural basis for agonist and heat activation of nociceptor TRPM3 - Nature Structural & Molecular Biology
TRPM3 is an ion channel that helps the body sense heat and contributes to pain. The authors show that both heat and small chemical molecules switch it on through similar changes inside the protein.
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Phil Biggin @philbiggin.bsky.social · 23/10/2025
Pleasure to be part of this work www.pnas.org/doi/10.1073/... with Sandip Basak at NTU where we show asymmetric gating in GLIC!
pnas.org
Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM | PNAS
Pentameric ligand-gated ion channels (pLGICs) are vital neurotransmitter receptors that are key therapeutic targets for neurological disorders. Alt...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 20/10/2025
Happy to share our new review of kainate receptor structure and gating. www.frontiersin.org/journals/pha...
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Da-Neng Wang @danengw.bsky.social · 24/09/2025
Congratulations, Yifan, for the Anatrace Award! Yifan’s work on the TRPV1 structure with David Julius helped launch the Resolution Revolution in cryo-EM. Not just in membrane proteins—hardly any area of biophysics today has remained untouched by the techniques Yifan pioneered.
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Gabriela K Popescu @popstarlab.bsky.social · 24/09/2025
Cryo-EM snapshots of NMDA receptor activation illuminate sequential rearrangements | Science Advances www.science.org/doi/10.1126/...
science.org
Cryo-EM snapshots of NMDA receptor activation illuminate sequential rearrangements
Opening of the NMDA receptor involves bending of the helices lining the ion channel gate.
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Sazanov Lab @sazanovlab.bsky.social · 18/09/2025
How the twin-arginine translocase (Tat) system manages to transport folded proteins across membranes without any leaks? To answer this fundamental question we solved the first structure of TatB3C3 complex with bound cargo. Please check out new preprint! t.co/962Kj9pt6F
t.co
https://www.biorxiv.org/content/10.1101/2025.09.16.676506v1
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Ed Twomey @cryoet.bsky.social · 16/09/2025
🚨🧠🔬 A major breakthrough in molecular neuroscience: I am excited to share a new story from our lab, published in accelerated format today by @nature.com: "Delta-type glutamate receptors are ligand-gated ion channels" Read more here (free article link): rdcu.be/eGIKz
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sobolevsky.bsky.social @sobolevsky.bsky.social · 15/09/2025
www.nature.com/articles/s41...
nature.com
GluA4 AMPA receptor gating mechanisms and modulation by auxiliary proteins - Nature Structural & Molecular Biology
Vega-Gutiérrez et al. present cryo-electron microscopy structures of GluA4-containing AMPA receptors, which are key for brain signaling. They show GluA4-specific conformations and explain how subunit ...
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sobolevsky.bsky.social @sobolevsky.bsky.social · 11/09/2025
Happy to share the molecular mechanism of activation of kainate-subtype ionotropic glutamate receptor GluK2 in complex with auxiliary subunits Neto2. In both closed/apo and open states, ligand-binding domain (LBD) layer has 2-fold rotational symmetry! www.nature.com/articles/s41...
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Irina Talyzina @irinatalyzina.bsky.social · 01/12/2024
Happy to share our new review on the structural pharmacology of TRP channels! Check out the supplementary table, which includes a list of all ligands, corresponding PDBs of complexes with TRP channels, and reported affinity values. www.sciencedirect.com/science/arti... #ionchannel #TRPchannel (1/5)
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