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Posts by James A. Letts

Video

How do cells convert mechanical information into a molecular process? The @alushinlab.bsky.social has captured the first snapshot of a mechanical signaling complex in action, findings in @nature.com that have implications for disorders related to myosin dysfunction.

🔗: https://bit.ly/41Kshjw

12 hours ago 28 14 0 0
Video

Our latest work on shape-programmable tissues is out in @science.org. By positioning topological defects in cellular nematics, we encode frustrated 2D force fields that relax into predictable 3D shapes. Collaboration with Marino Arroyo’s lab, led by @pauguillamat.bsky.social at @ibecbarcelona.eu.

5 days ago 176 64 7 4
A 3D model of DNA. Text says RSB training, an introduction to CryoEM, Tuesday 7 July, 9:30-16:30, The University of Leicester

A 3D model of DNA. Text says RSB training, an introduction to CryoEM, Tuesday 7 July, 9:30-16:30, The University of Leicester

Are you looking for a training course that will provide you with an introduction to cryoEM and its applications in structural biology ? Then join us in July!

📆 Tues 7 Jul, 9:30-16:30, University of Leicester

Book your place: my.rsb.org.uk/item.php?eve...

#Training #CryoEM

5 days ago 4 3 0 0

Our paper on the proton-driven secondary active #transporter SbmA for antimicrobial peptides is finally out! We used #cryoEM, #EPR, #MD to show that it resembles and undergoes conformational changes like #ABC transporter TMDs consistent with an alternating-access transport mechanism.

6 days ago 5 4 1 0

Across scales from cells🦠 to atoms⚛️ – We reveal how anaerobic #bacteria break down very stable aromatic compounds found e.g. in oil spills 🛢️ #Bioremediation #TeamTomo 🧪 🧶🧬 🔬

Awesome collab with Lena, Matthias, @schullerjm.bsky.social @rnfr2d2.bsky.social @tomaspascoa.bsky.social @tamb-o.bsky.social

1 week ago 79 25 1 2
a simplified evolutionary tree of eukaryotes with pictures of various microbes

a simplified evolutionary tree of eukaryotes with pictures of various microbes

New #ISEPpapers #preprint by @deemteam.bsky.social: Re-evaluating the eukaryotic Tree of Life with independent phylogenomic data www.biorxiv.org/content/10.6...

#Protists #Microbes #Evolution #Eukaryotes #TreeOfLife #Phylogeny #Phylogenomics #Bioinformatics #Algae

1 week ago 66 28 1 3

How do “LEGO-like” electron-bifurcating modules combine to drive degradation in BTEX-contaminated ecosystems?

Check out our latest preprint, where we use cryo-EM and cryo-ET to reveal how the 1 MDa BCRII complex powers extremely endergonic aromatic ring reduction.
www.biorxiv.org/content/10.6...

1 week ago 27 14 1 1
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Video

One of biggest mysteries in biology: how did complex eukaryotic cells evolve from simple microbes? ~1.8 billion years ago, an archaeal cell likely merged with a bacterium to form the first eukaryotic cell, but can we ever find direct evidence of this transformative event? 🦠 🚶‍♂️

1 week ago 107 39 3 6
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Structure of Mycobacterial NDH-2 Bound to a 2-Mercapto-Quinazolinone Inhibitor Mycobacterial type II NADH dehydrogenase (NDH-2) is a promising drug target because of its central role in energy metabolism in Mycobacterium tuberculosis and other pathogens, and because it lacks a k...

Now published J. Med. Chem! @zestytoast.bsky.social's structure of type II NADH dehydrogenase from mycobacteria. A promising drug target for TB & other mycobacterial infections, Yingke demonstrates how an inhibitor can block transfer of electrons from NADH to the ETC.
pubs.acs.org/doi/full/10....

1 year ago 25 11 2 0
Discovery of inhibitors of the Pseudomonas aeruginosa NADH:ubiquinone oxidoreductase (NQR) that hinder virulence factors The growing threat of antimicrobial resistance has created an urgent need to identify novel therapeutic targets in bacteria. The NADH:ubiquinone oxidoreductase (NQR) is a potential target in a number of bacteria that transfers electrons from NADH to ubiquinone while pumping ions from the cytoplasm to the periplasm. In most species, this complex pumps sodium ions, whereas in Pseudomonas aeruginosa it pumps protons, thereby functioning as a member of the electron transport chain. Using a strain of PAO1 with the NQR knocked out, we demonstrate that the NQR complex plays a crucial role in the motility and biofilm development virulence factors in P. aeruginosa. We develop and execute a high-throughput inhibitor screen to identify and confirm compounds that inhibit NADH oxidation by this complex. Using single-particle cryogenic electron microscopy (cryoEM), we determine high-resolution structures of the NQR complex, both inhibitor-free and bound to one of the confirmed hits from our screen, demonstrating that it binds to the ubiquinone binding site. These structures provide insight into conformational dynamics controlled by binding at the ubiquinone site, with potential implications for the coupling between electron transfer and proton pumping in this complex. Biofilm development and motility assays with selected compounds from the screen show that they affect these virulence factors similarly to the NQR knockout. ### Competing Interest Statement The authors have declared no competing interest. Cystic Fibrosis Canada, https://ror.org/05b6dcx13 LKSIoV and University of Alberta Faculty of Medicine and Dentistry Startup funding Striving for Pandemic Preparedness – The Alberta Research Consortium Canada Research Chairs Canadian Institutes of Health Research, https://ror.org/01gavpb45 LKSIoV Research Support and Innovation Grant

In the first preprint from the lab, @sandaru-ileperuma.bsky.social demonstrates that the P. aeruginosa NQR complex supports virulence factors and identifies inhibitors of this complex. He also uncovered some interesting NQR dynamics controlled at the substrate binding site. tinyurl.com/yush599n

1 month ago 14 8 1 0
Video

I am excited to share our most recent work collaborating with @centriolelab.bsky.social and @stearnslab.bsky.social to look at the ciliary base of mammalian multiciliated cells w/ cryo-ET, XL/MS, and U-ExM www.biorxiv.org/content/10.6...

2 weeks ago 125 62 3 7
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PDB101: Molecule of the Month: Insect Odorant Receptors Protein complexes that allow insects to detect a wide variety of volatile compounds

April's Molecule of the Month: Insect Odorant Receptors
These protein complexes allow insects to detect a wide variety of volatile compounds, from clove oil to DEET

3 weeks ago 7 4 0 0
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#Ichthyosporea are not just the 5–6 species we and others have helped establish as models. Our recent synthesis suggests that ~95% of their species-level diversity remains uncultivated. In other words, we still know only a fraction of the map! #protistsonSky @ibe-barcelona.bsky.social @prbb.org

4 weeks ago 26 10 1 0
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Excited to share our new paper in @natcomms.nature.com !
Here, we present the cryo-EM structure of the Cytc₆:PSI complex from Chlamydomonas reinhardtii👇
www.nature.com/articles/s41...

3 weeks ago 36 9 1 3

Added custom menus, including one to quickly add common monomers (detergents, buffers etc):

3 weeks ago 42 9 2 0
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Video

Added a little script to chimerax-trimmings to automate the creation of panels for model-map fit figures.

It zones the map around (by default) 40aa parts of each chain (but doesn't cut in the middle of helices). Saves each as a png, metadata to csv.

Saves each view as a scene for tweaking views.

3 weeks ago 46 8 2 2

Our work with the Brun lab on the in situ architecture of the Caulobacter crescentus Tad pilus machine is published in mBio. Amazing collaborative effort led by James Iarocci @jamesiarocci.bsky.social

4 weeks ago 15 12 1 1
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Structural energetics of cold sensitivity - Nature Data from cryogenic electron microscopy combined with hydrogen–deuterium exchange mass spectrometry inform a mechanism for cold-evoked activation of the TRPM8 channel, providing a structural and ...

Wow!
Structural energetics of cold sensitivity
www.nature.com/articles/s41...

4 weeks ago 15 9 0 0
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Excited to share our work on the structure and function of cytoplasmic lattices within mouse embryos. A collaborative effort with @niakanlab.bsky.social and work led by @kashishsingh.bsky.social and @inaharasimov.bsky.social . It is now out on BioRxiv: www.biorxiv.org/content/10.6...

4 weeks ago 190 77 6 9

Happy to share my first adventure in #TeamTomo in collaboration with the talented @inaharasimov.bsky.social. It was a fun experience experience with a lot of learning along the way.

4 weeks ago 42 12 1 0
Video

Finally got around to porting my coot-trimmings scripts over to Coot 1... only the hotkeys are working (nothing requiring creating a custom menu or GUI dialog), but I've added a couple of new ones, e.g. copy/pasting ligands.

Check it out & let me know what you think! 😊

github.com/olibclarke/c...

1 month ago 42 10 4 2
Schematic overview of crista shaping components in traditional and unconventional model organisms. (A) The MICOS in yeast (left) and T. brucei (right). Conserved proteins directly involved in membrane bending are shown in green, conserved proteins with an indirect or unclear involvement in membrane bending are shown in red, T. brucei-specific proteins are shown in yellow if directly involved in membrane bending, or in purple if they have an indirect effect. Numbers refer to the respective MICOS components: MIC60, MIC19, MIC10, MIC12, MIC26 and MIC27 in yeast, and MIC24, MIC34, MIC40, MIC10-1, MIC10-2, MIC20, MIC17, MIC32 and MIC16 in T. brucei. (B) Schematic figure of ATP synthase characteristics in yeast, T. brucei, T. gondii and P. falciparum. Dimeric ATP synthase structures have been solved for yeast, T. brucei and T. gondii, revealing dimer angles of 86°, 60° and 19°, respectively. For P. falciparum, the dimer angle is unknown. The different oligomerization states observed in these organisms are associated with different cristae shapes. In yeast, dimer rows produce lamellar cristae; in T. brucei, helical arrays of dimers produce discoidal cristae; in T. gondii, hexameric oligomerization generates bulbous cristae. The oligomerization state of P. falciparum ATP synthase is unknown (indicated by the question mark) but P. falciparum has been shown to have bulbous morphology of cristae.

Schematic overview of crista shaping components in traditional and unconventional model organisms. (A) The MICOS in yeast (left) and T. brucei (right). Conserved proteins directly involved in membrane bending are shown in green, conserved proteins with an indirect or unclear involvement in membrane bending are shown in red, T. brucei-specific proteins are shown in yellow if directly involved in membrane bending, or in purple if they have an indirect effect. Numbers refer to the respective MICOS components: MIC60, MIC19, MIC10, MIC12, MIC26 and MIC27 in yeast, and MIC24, MIC34, MIC40, MIC10-1, MIC10-2, MIC20, MIC17, MIC32 and MIC16 in T. brucei. (B) Schematic figure of ATP synthase characteristics in yeast, T. brucei, T. gondii and P. falciparum. Dimeric ATP synthase structures have been solved for yeast, T. brucei and T. gondii, revealing dimer angles of 86°, 60° and 19°, respectively. For P. falciparum, the dimer angle is unknown. The different oligomerization states observed in these organisms are associated with different cristae shapes. In yeast, dimer rows produce lamellar cristae; in T. brucei, helical arrays of dimers produce discoidal cristae; in T. gondii, hexameric oligomerization generates bulbous cristae. The oligomerization state of P. falciparum ATP synthase is unknown (indicated by the question mark) but P. falciparum has been shown to have bulbous morphology of cristae.

In their Review, Silvia Tassan-Lugrezin, Silje Debets, Laura van Niftrik, Taco Kooij & Irina Bregy compare crista across Euglenozoa, Alveolata & Opisthokonta to delineate evolutionarily conserved mechanisms underpinning a general model for crista formation.

journals.biologists.com/jcs/article/...

1 month ago 5 2 0 0
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Snapshots of the dynamic basis of NTSR1 G protein subtype promiscuity - Nature Time-resolved cryo-electron microscopy during activation of Gαi1βγ and Gα11βγ heterotrimers bound to NTSR1 enables isolation of multiple transient complexes along the activation pathway and reveals structural motifs that stabilize these intermediates.

Nature research paper: Snapshots of the dynamic basis of NTSR1 G protein subtype promiscuity

go.nature.com/4rqJcSA

1 month ago 9 3 0 0
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Convergent and lineage-specific genomic changes shape adaptations in sugar-consuming birds High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummin...

In a new Science study, researchers find that some bird species share convergent evolutionary changes in key physiological traits and metabolic genes that enable their high-sugar diets. https://scim.ag/4bgMrpy

1 month ago 30 11 0 0
Video

At the center of every nuclear pore lies a mystery. Here, clumps of proteins wiggle disordered tails around like seaweed. How do they drive a molecular machine that moves so many molecules in and out of the nucleus efficiently, with little room for error? www.quantamagazine.org/disorder-dri...

1 month ago 37 13 0 1
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Long-lost page of Archimedes’ writings rediscovered in France The discovery adds to the Archimedes Palimpsest, an important medieval manuscript containing texts from the Greek mathematician Archimedes

The discovery adds to the Archimedes Palimpsest, an important medieval manuscript containing texts from the Greek mathematician Archimedes

1 month ago 43 10 1 0
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'Virtual cell' captures most-basic process of life: bacterial division Researchers simulated nearly every molecule in a bacterial cell — and then watched the cell grow and reproduce.

For the first time, researchers have simulated nearly every chemical reaction in a living bacterial cell

go.nature.com/4lrAulM

1 month ago 80 30 0 2
Figure 1. Cryo-EM of abundant protein complexes in native membranes.

Figure 1. Cryo-EM of abundant protein complexes in native membranes.

Figure 2. Cryo-EM of membrane proteins in vesicles.

Figure 2. Cryo-EM of membrane proteins in vesicles.

Figure 3. 3D reconstruction of V-ATPase in native synaptic vesicle membranes.

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.

Figure 4. Generation of membrane vesicles for structure determination of proteins in their native lipid bilayer.

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...

1 month ago 173 65 3 2

Please check out our new preprint! Using single cell analysis paired with HCR to visualize transcript localization we have identified cell and tissue-specific expression of various genes encoding tubulins, kifs, and dyneins during neural crest development!

1 month ago 101 30 5 2
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Since last year, I've been making a RELION GUI that supports viewing, navigating and running jobs in a way completely compatible with the original RELION pipeline. Now it's working nicely for both SPA and tomography! Please try it out - github.com/hanjinliu/hi...

2 months ago 97 35 4 0