John Rubinstein

Structura Bio | Structura Bio

🚀 Hiring: Cryo-EM Application Scientist, Marketing!

Develop and deliver high-impact scientific marketing content, illustrate the value of new #CryoSPARC features and #cryoEM advances, and help scientists understand how our tools can help solve their problems.

structura.bio/careers/appl...

Really fun collaboration with Roman Melnyk from The Hospital for Sick Children Research Institute and Peter Dosa from University of Minnesota, making synthetic bile acids to be gut-restricted prevents C. difficile infection in a preclinical mouse model

Opinion: Peanut allergies are plummeting in children, and you can thank science Early exposure has turned out to be one of the best prevention methods for allergies in kids

Peanut allergies are plummeting in children, and you can thank science. Early exposure has turned out to be one of the best prevention methods, by @picardonhealth.bsky.social www.theglobeandmail.com/opinion/arti... via @theglobeandmail.com

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...

Associate Professor (tenure) or Professor (tenure) Dr. Connie Eaves Chair in Cancer Stem Cell Research Academic Job Category Faculty Bargaining Job Title Associate Professor (tenure) or Professor (tenure) Dr. Connie Eaves Chair in Cancer Stem Cell Research Department School of Biomedical Engineering | ...

Apply for the 'Dr. Connie Eaves Chair in Cancer Cell Research' at UBC. Come join the dynamic research community in Vancouver 🇨🇦!

With the Wilmanns lab @embl.org we reveal cryoEM structures of an essential, bifunctional acyl-CoA carboxylase from mycobacteria. @wertheimufscripps.bsky.social

This ~ 600 kDa enzyme is asymmetric, rotatory, has unusual stoichiometry, and unique E5 subunits.

www.biorxiv.org/content/10.1...

Never ceases to amaze me how structures reveal their secrets to multiple groups at nearly the same instant.
Congratulations to @luizcarvalholab.bsky.social and the Willmann's lab on their structures of the long chain acyl-CoA carboxylase complex!!
Will be interesting to compare.

Hydrophilic metformin and hydrophobic biguanides inhibit mitochondrial complex I by distinct mechanisms - Nature Structural & Molecular Biology He, Teng and Yang et al. report how metformin, the widely used antidiabetic drug, inhibit its target, the respiratory complex I, through a distinct state-dependent, inhibitor trapping mechanism, thus ...

How does the well tolerated anti-hyperglycemic drug #metformin inhibit mitochondrial complex I?
In our new paper, we use structures, MD and kinetics to show that metformin inhibits by a distinct mechanism that more hydrophobic, less well tolerated, biguanides.
www.nature.com/articles/s41...

Assembly, architecture and functional roles of microbial surface layers - Nature Reviews Microbiology Surface layers (S-layers) are ubiquitous protein assemblies that coat prokaryotic cells, with their functional roles increasingly coming into focus. In this Review, Isbilir and colleagues discuss rece...

Assembly, architecture and functional roles of microbial surface layers

Review article published in @natrevmicro.nature.com with @bupbuse.bsky.social, Andriko von Kügelgen and @vikramalva.bsky.social.

S-layers are everywhere!

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

A Man Took a Bus for a Joyride. Turns Out, He’s Not a Bad Driver. The incident in Hamilton, Ontario, ended safely with an arrest and no injuries (and all fares paid).

When a man hijacked a bus in Hamilton, Ontario, on Tuesday, the potentially catastrophic scenario ended happily. It turns out he was a pretty decent bus driver. He made regular stops to pick up passengers, the police reported. At one point someone tried to board with an expired bus pass. No dice.

Exciting to see a new compound showing promise against malaria.

As drug resistance grows, mosquito ranges expand & public health resources remain limited, the need for new treatments has never been greater.

tinyurl.com/42wb2efe by @kakape.bsky.social
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As always with our Mycobacterial work, all cryo-EM maps and atomic models are scheduled for immediate release by the wwPDB (@rcsbpdb.bsky.social @pdbeurope.bsky.social etc)

Oops, the picture of mycolic acids (from en.wikipedia.org/wiki/Mycolic...) in the previous skeet isn't displaying properly. Here it is again.

Cryo-EM maps and atomic models of the biotin-containing 3-methylcrotonyl-CoA carboxylase (MCC) complex and long-chain acyl-CoA carboxylase (LCC) complex

New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz

Chemical structures of mycolic acid (from wikipedia) showing different modifications of the myromycolate chain.

Thanks! Yes, lots of great work has been done on related complexes!
The mycobacterial LCC is pretty weird compared to the others, though: it has one type of subunit (AccD5) for acetyl/propionyl-CoA and another (AccD4) for very long chain acyl-CoA, used to form the alpha branch of mycolic acid:

Cryo-EM map (left) and atomic model (middle and right) showing that the uncharacterized proteins MSMEG_0435 and 0436 bind the LCC complex. These proteins were identified with ModelAngelo and FoldSeek and also detected by mass spectrometry of the sample.

Interestingly, Yingke found some complexes bound to uncharacterized proteins MSMEG_0435 & 0436 (Rv0263c & 0264c in M. tuberculosis). A recent preprint from Carl Nathan shows that Rv0263c is needed for Mtb survival during transmission, suggesting it modulates mycolic acid synthesis in TB transmission

A structure with short- and long-chain acyl-CoAs shows how the two types of carboxyltransferase (CT) subunit distinguish acyl-CoAs: the short-chain CT subunit binds CoA but can’t accommodate a long acyl chain; the long-chain CT subunit binds long acyl chains but doesn’t interact strongly with CoA.

Adding short-chain acyl-CoA substrate (plus ATP & bicarbonate) causes biotin carboxyl carrier protein (BCCP) domains to travel between biotin carboxylase (BC) domains, which load a carboxyl group onto the BCCP biotin, and the carboxyltransferase (CT) domain, which transfers it to the acyl-CoA.

Assay showing that the LCC complex has propionyl-CoA carboxylase activity (left). A cryo-EM map with propionyl-CoA (middle and right) shows where the short-chain acyl-CoA binds in the AccD5 subunit.

The MCC complex is well studied, but the long-chain carboxylase (LCC) complex isn’t, and is essential for making mycolic acid for the mycobacterial cell wall. The LCC complex carboxylates both long-chain and short-chain acyl-CoA. A structure with propionyl-CoA shows how it binds short-chain acyl-CoA

Cryo-EM maps and atomic models of the biotin-containing 3-methylcrotonyl-CoA carboxylase (MCC) complex and long-chain acyl-CoA carboxylase (LCC) complex

New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz

I was a PhD student at LMB at the time and remember it well. Ribosome breakthroughs every few months. New students and postdocs with Venki would join his lab and have their structures published on the cover of Nature or Science within the year.
It was really freakin' annoying!
🥰

SCIENTIST – Developmental, Stem Cell & Cancer Biology Program - Toronto (City), Ontario (CA) job with The Hospital for Sick Children - Developmental & Stem Cell Biology Program | 12848200 Discovery-based and/or translational research using model organism genetics and/or stem cell and organoid platforms to study paediatric cancer.

Fantastic opportunity at The Hospital for Sick Children. Please repost. www.nature.com/naturecareer...

Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator Nature Communications - Here, the authors present the 3.7 Å cryoEM structure of native sodium efflux pump PfATP4 from Plasmodium falciparum, revealing a bound protein that they term...

Learn how our hunt for the native structure of top antimalarial target PfATP4🧂led to the discovery of PfABP, an unknown essential binding partner, out now! @natcomms.nature.com 👉 rdcu.be/eLRlH 🦠🔬❄️

A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria

🚀 Introducing fully automated data processing for repeat-target #cryoEM.

Using new tools in #CryoSPARC, it is now possible to obtain resolutions & map quality equal to or better than manual processing, with zero user intervention.

Preprint: www.biorxiv.org/content/10.1...

End-to-end automation of repeat-target cryo-EM structure determination in CryoSPARC https://www.biorxiv.org/content/10.1101/2025.10.17.682689v1

Nominations for the June Almeida award for Mid/Senior-Career Women in Cryo-EM are now open! Submit your nomination via this link www.biophysics.org/awards-fundi... by November 14th to recognize an exceptional woman in our community.

Structural basis of T-loop–independent recognition and activation of CDKs by the CDK-activating kinase Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation o...

Now out in Science! Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. In @vcushing.bsky.social's magnum opus, we use #cryoEM to figure out how the CDK-activating kinase recognises CDKs to fully activate them - a key step in cell cycle control.
www.science.org/doi/10.1126/...

9 days to go:
* 2 x open positions!
* Exceptional environment, competitive start-up package
* University of Toronto appointments
* Toronto has great (and peaceful) quality of life!

Come join us at @westernu.ca: Chair, Department of Medical Biophysics: www.uwo.ca/facultyrelat...

Congratulations, Jason!