iiinova — where your digital self keeps evolving

Huge thanks to every lab and collaborator who made this possible, a genuinely multi-scale effort from atoms to organisms, and specially to the ERC Synergy grant that made this collaboration possible @erc.europa.eu 9/n

The consequences: axonal defects, and, in behavioral assays, increased susceptibility to seizures. Removal of this small structural module in MTCL1 ripples all the way up to circuit-level physiology. 8/n

Does this matter in a whole organism? In zebrafish, we selectively disrupted the C-MTBD domain. This was enough to make MTCL1 lose its precise localization at the axon initial segment, a key hub for neuronal signaling, and to selectively affect acetylated MT populations. 🐟🧠 7/n

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We tested this with in vitro reconstitution, cell-based assays, and all-atom molecular dynamics simulations. MTCL1 robustly increases acetylation when present during MT growth, and its reshaping of the K40 loop measurably improves recognition by αTAT. 6/n

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Why would that matter? Acetylation is added by an enzyme, αTAT, that needs access to K40, facing the MT lumen. We hypothesized that MTCL1 might be helping facilitate that access, directly assisting αTAT in finding and modifying its tubulin target. 5/n

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The twist: when MTCL1 binds tubulin during MT assembly instead, we saw something new. An extra segment of MTCL1 reaches into the MT's lumen and reshapes the loop containing the K40 acetylation site, making it more flexible. 4/n

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We found that MTCL1 is a key link between them. Using cryoEM 🔬❄️, we show its C-MTBD domain binds and stabilizes pre-assembled MTs. But that alone didn't explain why MTCL1-coated MTs are so consistently enriched in acetylation, a mark of long-lived MTs. 3/n

Microtubules can be regulated by proteins that bind and remodel them (MAPs), and by chemical marks written onto tubulin itself (the "tubulin code"). Both matter, but how these two layers communicate and integrate with each other is poorly understood. 🤔 2/n

Nogales Lab @nogaleslab.bsky.social · 29/06/2026

🧵 New paper alert! Today on bioRxiv, we show how a microtubule (MT) associated protein, MTCL1, links 2 regulatory layers: mechanical MT stabilization and writing of then tubulin code. A multi-lab effort driven by Juan Perez-Bertoldi and Julie Dang spanning atoms to organisms. 1/n

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Excited to share our new preprint with the Yildiz and Janke labs on how Ndc80 and Ska complexes cooperate on microtubules through a SKA3 tether and tubulin tail interface to stabilize attachment! Congrats to Ju and Ipsita for leading this exciting study! www.biorxiv.org/content/10.6...

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Nogales Lab @nogaleslab.bsky.social · 24/05/2026

Congrats to Ana Galic and Kevin Li, who just graduated with honors in MCB @berkeleymcb.bsky.social, and to the brand new Dr. Trinity Cookis @trinitycookis.bsky.social 👨‍🎓👩‍🎓👩‍🎓🤩. Very best wishes for your next endeavors 💝

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Nogales Lab @nogaleslab.bsky.social · 16/04/2026

Congrats to my @berkeleymcb.bsky.social colleague Andy Martin, who just received the Dorothy Crowfoot Hodgkin Award of the @proteinsociety.bsky.social. Andy's studies have made the proteasome one of the best understood molecular machines in biology. Well deserved!!

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Nogales Lab @nogaleslab.bsky.social · 11/12/2025

An honor to share the closing Keynote session @CellBio2025. Thank you American Society for Cell Biology (ASCB) and EMBO for an amazing meeting and for making us feel part of a community of inspiring scientists.

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Nogales Lab @nogaleslab.bsky.social · 18/11/2025

Excited to share our new preprint in collaboration with Ahmet Yildiz's lab. Check out how our team uncovers a novel binding footprint and motor regulation mechanism for MAP9 Congrats to Burak Cetin and @aryantaheri.bsky.social www.biorxiv.org/content/10.1...

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Nogales Lab @nogaleslab.bsky.social · 14/11/2025

Delighted to present my trajectory and research to audiences ranging from high school students to researchers at Hong Kong Universities and Science Centers. Special thanks to my local ambassadors Zhoe and Emi for making my visit so special 🥰🥰

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Nogales Lab @nogaleslab.bsky.social · 14/11/2025

An honor and pleasure to be at the @HKLaureatesForum, a “meeting of inspirational minds” gathering @ShawPrize recipients 🏅 and young scientists. Inspirational to hear other laureates and interact with promising researchers curious about the world around them, big 🪐 & small 🧬

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Nogales Lab @nogaleslab.bsky.social · 14/10/2025

Thrilled to share our new cryo-ET preprint on astrocytes, a collaboration with @mengmengfu.bsky.social here at @ucberkeleyofficial.bsky.social, revealing the nm-scale cytoskeletal architecture of ramified astrocytes reminiscing in vivo morphology. Check out the cytoskeleton compartmentalization!

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Nogales Lab @nogaleslab.bsky.social · 19/07/2025

A unique honor to become a Foreign Member of the @royalsociety.org, together with my @ucberkeleyofficial.bsky.social colleague Stuart Russell and old friends like John Briggs, Asia Akhtar, Patrick Cramer or Ruth Lehmann. Learning about great science and science history was a real treat.

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Nogales Lab @nogaleslab.bsky.social · 19/07/2025

Very grateful to the Menéndez Pelayo International University for awarding me an honorary doctorate last Tuesday, July 8th, in the incomparable setting of the Magdalena Palace (Santander). On Monday I enjoyed a conversation with those interested in my career and science.

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Nogales Lab @nogaleslab.bsky.social · 05/07/2025

So proud of the smashing success of the International Course in Biophysics co-organized with my @berkeleymcb.bsky.social colleague Carlos Bustamante and University of Salamanca @usaloficial.bsky.social biophysal.org Course ends with a Keynote from Nobel Laureate Richard Henderson🥇

biophysal.org

BioPhySAL - First Salamanca International Advanced Biophysics and Structural Biology Course

First Summer International Advanced Biophysics and Structural Biology Course. Eva Nogales - Carlos Bustamante.

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Yesterday I had the pleasure to visit the Institute for Material Science in Madrid @icmm-csic.bsky.social. Thank you to Dr. Pedro Serana for his invitation to talk about cryo-EM and our latest microtubule studies 🧩🔬🧬

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I spent a wonderful day in the Universidad de Córdoba at an interactive breakfast with faculty and students and giving a science presentation. Lovely to meet its Chancellor, Manuel Torralbo, and my friend and past collaborator Prof. Tina Domínguez-Martín.

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It was an absolute pleasure to visit the IBiS, to meet its scientists, interact with its students, and visit beautiful Sevilla 🥰

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Excited to have participated in the Third Symposium of Physical Chemistry in the Universidad Autónoma de Madrid @uam.es last week and honored that the Prizes for best student talk and best posters carried my name 🥰☺️

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Que día tan emocionante volver a mi colegio en Colmenar Viejo y recibir el calor de sus profesores y sus alumnos. Gracias por darle mi nombre a vuestra biblioteca! 🥰

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Deeply touched and honored by the Universidad Autónoma de Madrid, my alma mater, (@uam.es) making me Doctor Honoris Causa. Thank you to the Department of Physical Chemistry for nominating me for this recognition. It was a memorable day for me and my family👩‍🎓

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Nogales Lab @nogaleslab.bsky.social · 23/05/2025

Like a dream, my name next to that of @isabelallende.com, and to be recognized by Universidad Internacional Menéndez Pelayo UIMP. Soon after, Irene Vallejo @irenevalmore.bsky.social will receive the same honor. I feel proud to be linked to these truly inspiring, talented women! Thank you UIMP!

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This week our lab had a double celebration: 1) Eva’s election into the @royalsociety.org and 2) Zhenlin’s new job in Southern University of Science and Technology, China. He will be missed but we wish him success and joy in his independent career!

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A huge shoutout to our former grad student Susanne Kassube (now PI) for leading our lab’s original study back in 2013 and setting the stage for this work. If you’re interested, check out our preprint for more details and stay tuned for the full paper! 7/7

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Beyond a role in slowing down Pol II elongation, RECQL5 is known to decrease transcription stress. We propose that RECQL5 may help restart transcription from stalled Pol II by allosterically modulating Pol II’s translocation state. 6/7

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Nucleotide binding (AMPPNP or ADP) causes the RECQL5 helicase domain to undergo a conformational change, pulling on the DNA to induce Pol II to shift to a post-translocation state. Meanwhile, the IRI module seems to serve as a stable anchor for RECQL5 binding. 5/7

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The high resolution of our structures also enabled us to ask how RECQL5 affects Pol II, in particular its translocation state on a DNA/RNA scaffold. We found that Pol II occupies different translocation states when RECQL5 helicase is in its apo vs. nucleotide-bound form. 4/7

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We report high-resolution structures of Pol II elongation complexes with RECQL5, visualizing interactions between RECQL5, Pol II, and DNA, confirming its role as a transcriptional roadblock. This required extensive data processing, as RECQL5 is very flexible! 3/7

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Nogales Lab @nogaleslab.bsky.social · 12/01/2025

RecQ helicases help safeguard genome stability. In this family, RECQL5 stands out as the only one to interact with and inhibit RNA Pol II, and it’s been shown to help decrease transcription stress. We used cryo-EM to investigate the molecular basis for this mechanism. 2/7

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Our microtubule team at lunch with @ruizhangmt.bsky.social, who gave a spectacular seminar at UC Berkeley on his work on axonemes

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Nogales Lab @nogaleslab.bsky.social · 12/01/2025

The Cryo-EM: the next 50 years Symposium held yesterday at @ucberkeleyofficial.bsky.social was a smashing success!!

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These two distinct inhibition mechanisms are determined by the unique location of H3K4me3 and H3K36me3 along the histone H3 tail and target two essential requirements for efficient trimethylation of histone H3K27 to exclude PRC2 activity from actively transcribe genes

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The H3K4me3 modification binds to the well-characterized allosteric site in EED and can compete with allosteric activators of PRC2, however it lacks interactions with the EZH2 stimulatory response motif (SRM) and does not trigger allosteric activation like known PRC2 activators.

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The tail-disengaged state reveals a novel binding geometry between PRC2 and the nucleosome that is incompatible with catalytic activity

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We identified two states in cryo-EM analysis of PRC2 bound to H3K36me3 nucleosomes: 1) tail-engaged state that shows accommodation of modified H3 tails in the active site and 2) a tail-disengaged state that indicates H3K36me3 tails engage less efficiently with the PRC2 active site