David B. Sauer

It’s great to see people thinking about tracking errors in Fourier terms! EM_placement tries to infer effects of orientation bias from half maps, but it would be far better to do this directly in the reconstruction process. No surprise it’s people like ZO and Dominika doing this work!

Anyone know if I can submit a bug report to Toyota? Seems like an easy software fix.

Today I learned:
You can brick a Toyota EV with only the window defroster… if engaged before the traction battery 🤦‍♂️

🌟 WeINSPIREBio is hosting its first event!

On Dec 4, we’re running a webinar:

Structures of Success: Career Journeys of Women in Structural Biology

If you work in SB, drug discovery, or just like hearing career stories from brilliant people, join us! And please share 🙏🏼

lnkd.in/ewjD5WPt

#cryoEM

Structural basis of vilazodone dual binding mode to the serotonin transporter - Nature Communications The serotonin transporter (SERT) is a key antidepressant target. Here, authors present a cryo-EM structure where the antidepressant vilazodone spans the main SERT binding site toward a secondary ...

Yay! Our findings on the antidepressant drug vilazodone binding to the serotonin transporter (SERT) are out! We used cryo-electron microscopy and other advanced biophysics to provide data suggesting two high affinity binding poses.

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

Our latest work : Statins are used to lower plasma cholesterol but often come with muscle-related side effects. Using cryo-EM, we show how multiple statin molecules cooperate to bind RyR1, a calcium release channel mainly found in skeletal muscle.
nature.com/articles/s41...

The Swiss: Fluent in German, French, and English. Maybe Italian too.

This USAer: I know ‘Murican, un poco de Spanglish, and… Python 🤷‍♂️

PSA for people with NIH grant periods starting January 1st (including most NIGMS MIRAs): your RPPR is due Saturday, but they haven’t sent out the usual automated reminders, presumably due to the shutdown

Presenting our latest structural biology work and techniques at #PSDI2025

In this slide, the Gembody technology by @mingda-ye.bsky.social and colleagues!

A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

New in @science.org 🧬

What if an enzyme you thought you knew turned out to control metabolism in a completely new way?

We found that NUDT5 acts as a molecular handbrake on purine synthesis, reshaping how cells make DNA building blocks and respond to cancer drugs.

www.science.org/doi/10.1126/...

New online: New York City’s structural biology mosaic

Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...

Gluebodies Offer a Route To Improve Crystal Reliability and Diversity through Transferable Nanobody Mutations That Introduce Constitutive Close Contacts Design of modular, transferable protein assemblies has broad applicability and in structural biology could help with the ever-troublesome crystallization bottleneck, including finding robustly behaved protein crystals for rapidly characterizing ligands or drug candidates or generating multiple polymorphs to illuminate diverse conformations. Nanobodies as crystallization chaperones are well-established but still unreliable, as we show here. Instead, we show an exemplar of how robust crystallization behavior can be engineered by exploring many combinations (>200) of nanobody surface mutations over several iterations. Critically, what needed testing was crystallization and diffraction quality, since target–nanobody binding affinity is decoupled from crystallizability enhancement. Our study yielded multiple polymorphs, all mediated by the same interface, with dramatically improved resolution and diffraction reliability for some mutants; we thus name them ‘Gluebodies’ (Gbs). We further demonstrate that these Gb mutations do transfer to some other targets, both for achieving robust crystallization in alternative packing forms and for establishing the ability to crystallize a key early stage readout. Since the Gb interface is evidently a favored interaction, it may be broadly applicable for modular assembly; more specifically, this work suggests that Gbs should be routinely attempted for crystallization whenever nanobodies are available.

Gluebodies for improved crystal reliability and alternative crystal forms! (also inspiring Di-Gembody)

Great supports from @cmd.ox.ac.uk @rosfrankinst.bsky.social @diamondlightsource.bsky.social @davidbsauer.bsky.social

Out now in ACS Central Science! @pubs.acs.org
doi.org/10.1021/acsc...

Spam conference emails finally made me chuckle!

Though the mass spec team does look a bit sketchy…

Amazing news!! Congrats KJ!!

For something new and different, I'll be speaking at the 2025 #PEGSEurope meeting in Lisbon about producing membrane proteins at scale.

Looking forward to the conversations!

PhD project alert: the excellent MIBTP programme is open for applications. I am offering an exciting project on endogenous membrane protein complexes, jointly supervised with @alangoddard.bsky.social. Please spread the word!
warwick.ac.uk/fac/cross_fa...

More exciting Cationic Amino acid Transporters: The more promiscuous and pH-regulated SLC7A4.

Beautiful work from our friends in the Newstead and @philbiggin.bsky.social labs down the hill of @oxfordbiochemistry.bsky.social

www.researchsquare.com/article/rs-7...

Carve that last sentence in stone, alongside “if you can’t see your particles they are not there” and “if you can’t see your ligand do not try to just model it anyway”

Shockingly disappointed in this impulse buy. So many simple chemistry mistakes…

Love an easy read, and 100% support accessible science, but this is more frustrating than fun.

Keeping my identity secret requires two hotspots!

Na-Na-Na-Na-Na-Na-Na-Na…

Small molecule inhibitors of the NorA multidrug efflux pump potentiate antibiotic activity by binding the outward-open conformation Antibiotic resistance is among the greatest threats of the modern era. Multidrug efflux pumps expel antibiotics from bacterial cells and present a particular challenge by conferring resistance to a br...

A new, small molecule inhibitor to NorA that increase fluoroquinolone efficacy against Staph. With everything: screening, med. chem., and CryoEM!

doi.org/10.1101/2025...

SLC45A4 is a pain gene encoding a neuronal polyamine transporter - Nature The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.

Our paper on SLC45A4 is out now in @nature.com! The orphan SLC45A4 transporter is a polyamine transporter involved in chronic pain signalling!

We are hiring a Postdoc in membrane protein cryo-EM at the University of Georgia. Looking for candidates with expertise in membrane protein purification and biochemistry. Fully funded for up to 5 years. Join us in Athens, GA. Apply: camilo.perez@uga.edu

Quote from Dr. Mingda Ye, University of Oxford, highlighting the collaborative breakthrough in cryo-EM imaging of small proteins: “This idea was initiated when solving sub-50kDa protein structures by cryo-EM was almost impossible. To break this barrier, many world-class scientists in different fields have combined forces and it is a great honour to work with them to bring this game-changing tool into reality!” The background diagram outlines the scientific workflow used in the study.

Exciting work from the Franklin, @ox.ac.uk, and @diamondlightsource.bsky.social has led to a new method for imaging small proteins (<50 kDa) using cryoEM. By using bifunctional, bispecific nanobody scaffolds, the team have successfully solved the smallest protein structure to date (14 kDa).

Covalently constrained ‘Di-Gembodies’ enable parallel structure solutions by cryo-EM - Nature Chemical Biology Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely...

Di-Gembodies (dimerized nanobodies) for improved and duplexed CryoEM of small and challenging targets!

A collaboration of @cmd.ox.ac.uk, STRUBI, @diamondlightsource.bsky.social, @rosfrankinst.bsky.social

Out now in Nature Chemical Biology @natchembio.nature.com

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

Colin Kleanthous' fundraiser for Motor Neurone Disease Association Help Colin Kleanthous raise money to support Motor Neurone Disease Association

My wonderful colleage Colin Kleanthous is raising money for the MND association. Please support Colin in this worthy endeavor! www.justgiving.com/page/colin-k...
(Please repost!)

Faculty and academic positions – University of Copenhagen

Looking for a Post doc position in Structural Biology? We are hiring!
See post here:
jobbank.dk/job/2850337/...

The task is to continue our endeavor in solving cryo-EM structures of the human dopamine transporter. See: doi.org/10.1038/s415...
Thanks to the Novo Nordisk Foundation for funding.

Large-scale experimental assessment of variant effects on the structure and function of the citrate transporter SLC13A5 Functional and mechanistic analysis of all single–amino acid variants in the human citrate transporter SLC13A5.

Wow! Deep Mutational Scan of NaCT!!

www.science.org/doi/10.1126/...

Valuable to biochem. understand NaCT folding & function, and clinical VUS in SLC13A5-Epilepsy

Beautiful study and Herculean effort by Wen-An Wang and REsolution colleagues in @supertifurgalab.bsky.social at @cemm.oeaw.ac.at

Closing soon!

Please apply if you are interested in targeting membrane proteins with new therapeutics!