Matthew Bowler

Great work from post-doctoral fellow @joanzone.bsky.social:

New preprint on identifying active structures of protein kinases -- capable of binding ATP, Mg ions & especially substrates -- +modeling all 437 human catalytic protein kinase domains in their active conformation.

doi.org/10.64898/202...

Job opening for Research Group Leader in Structural Studies at MRC Laboratory of Molecular Biology, focusing on macromolecular structures.

Are you a structural biologist pushing the boundaries of molecular science with an ambitious research programme?
Join our Structural Studies Division as a tenure-track Group Leader, with core funding, world-leading facilities & enthusiastic colleagues.
Apply by 16 MAR
www.nature.com/naturecareer...

Please spread the word: the Structural Studies Division @mrclmb.bsky.social is looking for a new tenure-track, independent group leader with an exciting plan in any area of Structural (Molecular & Cell) biology, in discovery biology and/or methods development. 🥳

mrc.tal.net/vx/mobile-0/...

One week left to apply - get writing!

Structural Basis for the Subversion of MAP Kinase Signaling by an Intrinsically Disordered Parasite Secreted Agonist Pellegrini et al. show how a protein, GRA24, secreted by the causative agent of toxoplasmosis, directly activates a host MAP kinase signaling cascade (p38α). The structure of the complex provides a me...

And once again many thanks to my friend and colleague @hakimi.bsky.social for discovering the Toxoplasma protein GRA24 - it has a very tight binding KIM motif that we used to stabilise the MEK-ERK complex!
www.cell.com/structure/fu...

Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1 www.biorxiv.org/content/10.64898/2026.01.19.700303v1 #cryoEM

Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1 https://www.biorxiv.org/content/10.64898/2026.01.19.700303v1

Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1 https://www.biorxiv.org/content/10.64898/2026.01.19.700303v1

Wonderful support from Pauline Juyoux and Guy Schoehn IBS Grenoble on the amazing new CM02 microscope, @gervasiolab.bsky.social for wonderful MD studies!

✅ MEK1 binds ERK2 at multiple sites remote from the activation loop

✅ Molecular details of phosphorylation of the ERK2 activation loop tyrosine

✅ MEK1 can bind ERK2 in the absence of nucleotide - suggesting a processive mechanism

✅ ERK2 binding destabilises the regulatory A-helix of MEK1

Then HR-HAIR from @olibclarke.bsky.social really improved our reconstructions www.biorxiv.org/content/10.1...

HexAufoil grids from Chris Russo's group @mrclmb.bsky.social gave amazing results for this 86 kDa complex!

New Preprint alert! Excited to share our latest work on the #MAPKinases from stellar PhD student Jill von Velsen. First structures of the MAP2K MEK1 activating its substrate MAPK between 2.9 and 3.6A - amazing resolutions for such a small and mobile complex! www.biorxiv.org/content/10.6...

I'm looking forward to speaking at this course (and finally seeing my PhD-labmate @mattbowler.bsky.social's institute in Grenoble)!

Are you working on challenging projects in structural biology?

#EMBOMacromolecular will highlight the strategic use of cutting-edge protein structure prediction methods, and recent advances in in situ structural biology. Apply by 18 Feb to join us at EMBL Grenoble! 🧬

s.embl.org/mmo26-01-bl

Very pleased to be on the organizing committee of the EMBO course Structural Characterization of Macromolecular Complexes in 2026! We have a fantastic line up of speakers and tutors, please share widely!

👉apply here: www.embl.org/about/info/c...

Are you working on challenging projects in structural biology?

#EMBOMacromolecular will highlight the strategic use of cutting-edge protein structure prediction methods, and recent advances in in situ structural biology. Apply by 18 Feb to join us at EMBL Grenoble! 🧬

s.embl.org/mmo26-01-bl

Another amazing drug repurposing study from Silvia Diaz Martin Alexandre Bougdour Christopher Swale and @hakimi.bsky.social Very pleased to have supported the structural work on our favorite protein family - the kinases!

Structural and functional characterization of TgGSK3, a druggable kinase in Toxoplasma gondii - Nature Communications Researchers identify the cancer drug LY2090314 as a potent inhibitor of Toxoplasma gondii and Cryptosporidium and report the first crystal structure of the parasite kinase TgGSK3 bound to it, validati...

Nature Com. now live! 🎉 Silvia’s amazing PhD supervised by Alex “the Greatest” & Christopher’s big-bang contribution. Huge thanks to our stellar team & collaborators. We went fishing in the FDA pond and hooked LY2090314 🎣 Blocks GSK3 🎯in #Toxoplasma & #Crypto

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

For sure, Macron’s troubles are partly of his own making. But there is something immensely sad about a pro-European leader and standard-bearer for the democratic centre ending up with such a political mess

These results are truly impressive! But I do worry that #cryoEM is moving into a phase where progress is made by optimizing parameter settings for black box programs. The devil is often in the details, and I am not sure how this could be implemented in #relion, as stated, without more info.

Zeus had his Hydra ⚔️, now Toxoplasma has its own.

Meet Hydra: not a monster, but a brand-new protein domain.
It multimerizes like crazy & rewrites the chromatin landscape 🧬 in Toxoplasma.

Our team and colleagues from @embl.org #Grenoble just dropped the preprint 👉
www.biorxiv.org/content/10.1...

We believe that maintaining MAP kinase signaling when ATP levels have been depleted, for example under hypoxic conditions, that occur under a number of cell stresses, such as cancer and atherosclerosis, would be an advantage.

Using radiolabeled nucleotides @PaulineJYX was able to demonstrate clearly that the beta-phosphate is transferred to p38. She then also showed that the other MAP2Ks also show this property, but that RIP2K does not.

While preparing the MKK6-p38 complex for structural studies (science.org/doi/10.1126/sc…) we noticed that p38 was activated by MKK6 in the presence of ADP as well as ATP

In our new paper @asbmb.bsky.social JBC we detail our surprising discovery that the MAP2Ks can use ADP to phosphorylate their substrate MAPKs – driven by @paulineJYX @ErikaPellegri13 and @jvonvelsen

t.co/spLZbaz5Wk

An ISWI-related chromatin remodeller regulates stage-specific gene expression in Toxoplasma gondii - Nature Microbiology Toxoplasma gondii evolved two ISWI remodellers, TgSNF2h and TgSNF2L. TgSNF2h forms a complex that insulates active genes, regulates MORC-driven sexual commitment and ensures precise gene expression, s...

Thrilled to share my first paper, now out in
@natmicrobiol.nature.com! Huge thanks to my amazing supervisor @hakimi.bsky.social and everyone who contributed to this work!

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

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We are very happy. The Editors of Journal of Applied Crystallography have chosen figures from our article (journals.iucr.org/j/issues/202...) to feature as the cover image for the February 2025 issue. THANKS

RIP Sine. She hired me as beamline scientist on ID14 @esrfsynchrotron 17 years ago and was a great director putting automation to the fore ultimately leading to @ID30_MASSIF1