James A. Letts
@lettsscience.bsky.social
π€ 94
π₯ 191
π 15
pinned post!
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...
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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 ...
https://www.nature.com/articles/s41594-025-01710-6
3 months ago
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reposted by
James A. Letts
Arc Institute
about 8 hours ago
Finding one mutation that improves a protein is hard. Finding five that work together is exponentially harder. Today in
@science.org
, Hsu and Konermann labs present MULTI-evolve, a lab-in-the-loop framework that does it in just one machine learning-guided round.
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James A. Letts
cryoEM papers
about 7 hours ago
Cryogenic electron tomography by the numbers: Charting underexplored lineages in structural cell biology
pubmed.ncbi.nlm.nih.gov/41706896/
#cryoem
0
4
1
reposted by
James A. Letts
Phil Holliger
7 days ago
New paper from my group in
@science.org
: "A small polymerase ribozyme that can synthesise itself and its complementary strand"
www.science.org/doi/10.1126/...
Outstanding work by
@edogia.bsky.social
1
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reposted by
James A. Letts
Florent Waltz
10 days ago
Long in the making, but happy to present the Chlamydomonas chlororibosome! Cryo-ETπ¬reveals a large new domain on the small subunit, built from multiple extensions in conserved ribosomal proteins. bioRxiv π:
shorturl.at/q44tG
This suggests greater chlororibosome diversity than expected! 1/n π§΅
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Very happy to contribute a short section to this Methods in Molecular Biology regarding Eugleozoa. We describe large-scale Paradiplonema papillatum cultivation using carboys. Great work by postdoc Dong Woo Shin and a game changer for biochemical and structural work!
link.springer.com/book/10.1007...
10 days ago
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2
0
reposted by
James A. Letts
Gautam Dey
15 days ago
Thank you
@mollyherring.bsky.social
for the stunning showcase π Like what you see? Come ExM with us! Letβs flood the internet with microbial marvels π¦
#ProtistsOnSky
#MicroEvoSky
π§ͺπ¬π
@dudinlab.bsky.social
@centriolelab.bsky.social
@moorefound.bsky.social
@embl.org
@erc.europa.eu
@embo.org
add a skeleton here at some point
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33
reposted by
James A. Letts
Science Magazine
14 days ago
Zombosomes, large vesicles with cell-like qualities, can spread alpha-synuclein protein clumps from astrocytes to other astrocytes, neurons, and lab-grown brain tissues. Learn more:
https://scim.ag/4qSd1vP
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reposted by
James A. Letts
Quanta Magazine
14 days ago
Expansion microscopy may be the hi-res hero that many biologists have been craving.
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Expansion Microscopy Has Transformed How We See the Cellular World | Quanta Magazine
How physically magnifying objects using a key ingredient in diapers has opened an unprecedented view of the microbial world.
https://www.quantamagazine.org/expansion-microscopy-has-transformed-how-we-see-the-cellular-world-20260204/
0
25
11
reposted by
James A. Letts
Victor Tobiasson
22 days ago
LAST CALL! Come join me at Glasgow University for evolutionary structural biology! We have fully positions. Computational Postdoc:
www.jobs.gla.ac.uk/job/research...
Structural Postdoc:
www.jobs.gla.ac.uk/job/research...
Technician:
www.jobs.gla.ac.uk/job/technici...
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Technician
Job PurposeThe post holder will join the School of Infection and Immunity, supporting structural biology research under the supervision of Dr Victor Tobiasson (Principal Investigator).Β The applican...
https://www.jobs.gla.ac.uk/job/technician-5770250?source=gla.ac.uk
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5
3
reposted by
James A. Letts
Mari de Sautu
23 days ago
Check out our new preprint! We uncover the full molecular mechanism of rotavirus membrane penetration and cytosolic escape using cryo-ET, live-cell imaging, and single-molecule assays. (1/3) π
biorxiv.org/content/10.6...
2
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reposted by
James A. Letts
Structura Biotechnology
23 days ago
π CryoSPARC v5.0 BETA is here! Weβre excited to deploy another major
#CryoSPARC
release to help enable and accelerate
#cryoEM
data analysis. v5 has a redesigned underlying software system and many new features - highlights in thread! Full changelog:
cryosparc.com/updates/v5.0.0
1
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reposted by
James A. Letts
Nature Communications
about 1 month ago
Single-cell genomics reveals complex microbial and viral associations in ciliates and testate amoebae
#Symbiosis
#Protists
#GiantViruses
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Single-cell genomics reveals complex microbial and viral associations in ciliates and testate amoebae - Nature Communications
Protist microbiomes are poorly understood. Here, the authors analysed single protist cells to profile their microbiomes and viromes showing that these tiny eukaryotes serve as environmental hubs for hidden bacterial symbionts and diverse giant viruses.
http://dlvr.it/TQSfXF
0
6
1
reposted by
James A. Letts
Basil Greber
about 1 month ago
π π Atomic-resolution
#cryoEM
at 200 keV.
www.biorxiv.org/content/10.6...
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Atomic resolution cryo-EM at 200 keV
Atomic resolution in cryo-electron microscopy was first demonstrated six years ago. This was accomplished using 300 kV electron microscopes equipped with new hardware that provided narrower energy spr...
https://www.biorxiv.org/content/10.64898/2026.01.09.698548v1
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reposted by
James A. Letts
Journal of Cell Science
about 1 month ago
Isadonna Tengganu and Ke Hu develop transfection and ExM protocols for Chromera velia, enabling direct comparisons with its parasitic apicomplexan relative, Toxoplasma gondi.
journals.biologists.com/jcs/article/...
0
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reposted by
James A. Letts
The Rockefeller University
about 1 month ago
For decades, scientists have designed drugs to slow down or block enzymes, but Tarun Kapoor wondered if tackling some diseases requires the opposite approach. We spoke with Kapoor about why speeding up an enzyme is so difficult, and how his team is cracking this problem. See the full Q&A here:
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Scientists have gotten good at blocking enzymes to treat disease. Now can they speed them up? - News
Enzymes are the molecular machines that power life; they build and break down molecules, copy DNA, digest food, and drive virtually every chemical reaction in our cells. For decades, scientists have d...
https://www.rockefeller.edu/news/38871-scientists-have-gotten-good-at-blocking-enzymes-to-treat-disease-heres-what-they-need-to-learn-next/
0
7
4
reposted by
James A. Letts
Kaitlyn Abe
about 1 month ago
It is so exciting to see our LEA proteins playing a role in solving this insane structure. Amazing work to the authors!
add a skeleton here at some point
0
9
4
reposted by
James A. Letts
Ben Engel
about 1 month ago
The
#ChlamyDataset
is on the cover of
@cp-molcell.bsky.social
πΌοΈπ₯°! Read
@lifeonthewedge.bsky.social
's great threadπ§΅ for the inside scoopπ¨ on all the
#TeamTomo
developments already made possible since these 1829 tomos hit EMPIAR π§ͺ π§Άπ§¬ For more, here's the old preprint thread:
bsky.app/profile/cell...
add a skeleton here at some point
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36
10
reposted by
James A. Letts
Janet Iwasa
about 1 month ago
This was a really fun and interesting Molecule of the Month to do! Check out the article to see even more elaborate RNA-only structures.
add a skeleton here at some point
0
15
7
reposted by
James A. Letts
Journal of Cell Biology
about 2 months ago
Medina, Chang et al. of the
@nanigrotjahn.bsky.social
lab introduce a new method based on the Surface Morphometrics pipeline to measure global and local thicknesses of organellar
#membranes
from cellular cryo-electron tomography data.
rupress.org/jcb/article/...
#CryoET
0
29
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reposted by
James A. Letts
Miguel MΓ©ndez SandΓn
2 months ago
New preprint out! Using ~75k environmental OTUs + 77 fossil calibrations, we reconstructed a Proterozoic timeline of eukaryote evolution. Our results show crown eukaryotes were already diversifying >1.6 Ga, long before the first undisputed fossils (~1.05 Ga). π DOI:
www.biorxiv.org/content/10.6...
4
110
58
reposted by
James A. Letts
Arcadia Science
about 2 months ago
A free, open-access library of high-quality organism illustrations for science communication
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A free, open-access library of high-quality organism illustrations for science communication
We create vector graphics of model organisms and emerging biological research organisms to enhance our publications. Weβre sharing these editable graphics under a CC0 license for other scientists to...
https://doi.org/10.57844/arcadia-4gbv-pzkv
1
268
138
reposted by
James A. Letts
Katharina GeiΓler
2 months ago
Itβs out! Using cryo-ET in Dicty cells, we take a fresh in situ look at vaults. Surprisingly, we uncover vaults associated with ER and NE membranes, and find that many vaults enclose ribosomes in defined orientations, opening new avenues to their cellular function!
www.biorxiv.org/lookup/conte...
add a skeleton here at some point
2
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44
reposted by
James A. Letts
Paul Sigala
about 2 months ago
Happy to share a new preprint exploring the unusual biochemistry of a "weirdly" diverged cytochrome c in malaria parasites that exemplifies a lineage common to many apicomplexan parasites.
@uofubiochem.bsky.social
@uuhsresearch.bsky.social
@uofutahcihd.bsky.social
www.biorxiv.org/content/10.6...
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A Divergent Cytochrome c in Malaria Parasites with an Anomalously Low Redox Potential
Eukaryotic cytochrome (cyt) c is a highly conserved mitochondrial protein central to cellular respiration, featuring a covalently attached hexacoordinate heme whose redox potential is tuned by axial H...
https://www.biorxiv.org/content/10.64898/2025.12.23.696199v1
0
17
9
reposted by
James A. Letts
Maximilian Ganser
about 2 months ago
Finally, weβve solved a long-standing mystery: what tintinnid shells are actually made of: A new class of biomaterial formed by remarkable structural proteins unique to tintinnids. A major milestone after 3 years of work! Read about it in our preprint:
doi.org/10.64898/202...
#ProtistsOnSky
4
95
38
reposted by
James A. Letts
Florent Waltz
2 months ago
Final version is out! Our large-scale cryo-ET dataset π¬ of Chlamydomonas reinhardtii π¦ is now published in
@cp-molcell.bsky.social
Huge collaborative effort! So glad to see the community already using it to develop new resources & tools. Check it out here:
shorturl.at/z4i4c
#CryoEM
#CryoET
3
137
48
reposted by
James A. Letts
Rockefeller University Press
2 months ago
New
@jgp.org
study from Lopez-Mateos, Narang, &
@vyy-sf.bsky.social
@ucd-physiology.bsky.social
reveals potential of
#DeepLearning
methods to model multiple states of human voltage-gated sodium channels and their interactions with Ξ²-subunits and calmodulin.
rupress.org/jgp/article/...
#IonChannels
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0
3
2
reposted by
James A. Letts
Fabien Burki
2 months ago
Just on time for the holidays! Happy to share the published version of the discovery of leptophytes, a new deep-branching and widespread group of microalgae based on plastid MAGs (ptMAGs). Now with additional support from a mitochondrial MAG (mtMAG) of leptophytes.
www.nature.com/articles/s41...
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Identification of a deep-branching lineage of algae using environmental plastid genomes - Nature Communications
Here, the authors leverage data from the Tara Oceans expeditions to perform a phylogeny-guided plastid genome-resolved metagenomic survey and provide 660 non-redundant plastid genomes from marine alga...
https://www.nature.com/articles/s41467-025-67401-4
2
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25
reposted by
James A. Letts
Oli Clarke
2 months ago
very unusual - a tRNA regulated anion channel
add a skeleton here at some point
2
57
25
reposted by
James A. Letts
Basil Greber
2 months ago
Our latest paper on the molecular mechanisms of XPF-ERCC1 recruitment to SLX4-dependent DNA repair pathways has been published! Congratulations to first author Junjie Feng, and a heartfelt thank you to all our collaborators for their contributions to this study!
www.nature.com/articles/s41...
2
83
24
reposted by
James A. Letts
Kate Beckham
2 months ago
www.nature.com/articles/s41...
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AlphaFold predictions are valuable hypotheses and accelerate but do not replace experimental structure determination - Nature Methods
An analysis of AlphaFold protein structure predictions shows that while in many cases the predictions are highly accurate, there are also many instances where the predicted structures or parts of pred...
https://www.nature.com/articles/s41592-023-02087-4
0
25
15
reposted by
James A. Letts
cryoEM papers
2 months ago
Cryo-EM structures of plant Augmin reveal coiled-coil assembly, antiparallel dimerization, and NEDD1 binding
pubmed.ncbi.nlm.nih.gov/41387433/
#cryoem
0
2
2
reposted by
James A. Letts
Sven T. Stripp
2 months ago
Love the caption of Fig. 3 in this impressive preprint: "A Goodsell-esque 3D orthogonal rendering of an IsoNet2-processed FIB-milled tomogram of C. reinhardtii"
doi.org/10.64898/202...
Since I am no expert, what does the cryoET community think of IsoNet?
@cellarchlab.com
doi.org/10.1038/s414...
3
67
16
reposted by
James A. Letts
Maddy Seale
2 months ago
This week in
@science.org
Structural insight into the incorporation of far-red chlorophyll f in cyanobacterial photosystem I
www.science.org/doi/10.1126/...
#cyanobacteria
#plantscience
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Locating the missing chlorophylls f in far-red photosystem I
The discovery of chlorophyll fβcontaining photosystems, with their long-wavelength photochemistry, represented a distinct, low-energy paradigm for oxygenic photosynthesis. Structural studies on chloro...
https://www.science.org/doi/10.1126/science.ado6830
0
32
14
reposted by
James A. Letts
Ben Engel
2 months ago
Happy to share our fun team-up with
@centriolelab.bsky.social
&
@stearnslab.bsky.social
to reveal the architecture of the mammalian centrioleβs Distal Ring π. Very cool multiscale integration of
#UExM
ππ¬with
#CryoET
βοΈπ¬. Congrats to
@ebertiaux.bsky.social
&
@computingcaitie.bsky.social
#TeamTomo
π§ͺ
add a skeleton here at some point
0
53
18
reposted by
James A. Letts
Nature Structural & Molecular Biology
2 months ago
New online: Atomic models of the Toxoplasma cell invasion machinery
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Atomic models of the Toxoplasma cell invasion machinery
Nature Structural & Molecular Biology, Published online: 09 December 2025; doi:10.1038/s41594-025-01728-wZeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.
https://go.nature.com/4rOkTiP
0
21
9
reposted by
James A. Letts
UC Davis
2 months ago
Two researchers at UC Davis have been awarded a VinFuture Prize in recognition of their work developing self-cloning crops, a breakthrough for sustainable agriculture. Read more:
ucdav.is/4oJ41Hx
0
17
8
reposted by
James A. Letts
Anthony M. Bonacolta
3 months ago
Had a great time interviewing Dr. Lilach Sheiner (
@sheinerlab.bsky.social
) for the latest edition of ISOPβs Protistology Newsletter. Check it out here!
#ProtistsOnSky
#Toxoplasma
#Science
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ISOP member spotlight Lilach Sheiner
YouTube video by Protistologists
https://youtu.be/pkqBbtAhhuM?si=5lfeAfowsZRfxtEL
0
10
5
reposted by
James A. Letts
Trends in Biochemical Sciences
2 months ago
π Online now - the Review "Structural transport and inhibition mechanism of the mitochondrial pyruvate carrier" from Edmund Kunji (
@mrc-mbu.bsky.social
) and co.
#SLC54
#MPC
#EnergyMetabolism
#MembraneProteinStructure
#StructureBasedDrugDesign
Read it here π
authors.elsevier.com/sd/article/S...
1
8
6
reposted by
James A. Letts
Filip Van Petegem
3 months ago
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...
1
17
5
reposted by
James A. Letts
Quanta Magazine
3 months ago
Like a kangaroo, the dinoflagellate ππͺπ΅π©π’π³πͺπ΄π΅π¦π΄ π³π¦π¨πͺπΆπ΄ has a pouch. The pouch is called a phaeosome chamber, which houses symbiotic cyanobacteria (the orange cells). These cells have a free-loading roommate: an archaeal parasite.
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A Cell So Minimal That It Challenges Definitions of Life | Quanta Magazine
The newly described microbe represents a world of parasitic, intercellular biodiversity only beginning to be revealed by genome sequencing.
https://www.quantamagazine.org/a-cell-so-minimal-that-it-challenges-definitions-of-life-20251124/
0
50
13
reposted by
James A. Letts
FEBS Letters
3 months ago
β‘ How conserved is respiratory complex I (CI) across
#eukaryotes
β and where does
#evolution
leave its mark? This review by
@lettsscience.bsky.social
compares CI across seven lineages, revealing variation in core subunits and lineage-specific accessory proteins. β‘οΈ
doi.org/10.1002/1873-3468.70181
0
3
3
reposted by
James A. Letts
Quanta Magazine
3 months ago
Genome sequencing technology is introducing biologists to a world of quasi-life forms that theyβve never met before.
@jakebuehler.bsky.social
reports:
www.quantamagazine.org/a-cell-so-mi...
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A Cell So Minimal That It Challenges Definitions of Life | Quanta Magazine
The newly described microbe represents a world of parasitic, intercellular biodiversity only beginning to be revealed by genome sequencing.
https://www.quantamagazine.org/a-cell-so-minimal-that-it-challenges-definitions-of-life-20251124/
1
34
15
reposted by
James A. Letts
ISEP
3 months ago
Discovery of rare
#protist
reveals previously unknown branch of eukaryotic tree of life
phys.org/news/2025-11...
Rare microbial relict sheds light on an ancient eukaryotic supergroup
www.nature.com/articles/s41...
#Protists
#Microbes
#Evolution
#Eukaryotes
#TreeOfLife
1
20
4
reposted by
James A. Letts
Fabien Burki
3 months ago
Each such discovery is a game changer for our understanding of eukaryote evolution, and this paper is no exception. Meet Solarion, which displays yet again novel types of subcellular structures. Congrats to all authors on a fascinating story.
#protistsonsky
www.nature.com/articles/s41...
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Rare microbial relict sheds light on an ancient eukaryotic supergroup - Nature
The discovery of an unusual protist named Solarion arienae, which has a mitochondrial genome with some intriguing features, provides insight into the early radiation of eukaryotic groups.
https://www.nature.com/articles/s41586-025-09750-0
2
57
15
reposted by
James A. Letts
RΓ©mi Fronzes
3 months ago
Our latest T7SS study is now out in Science Advances! We solved the cryoEM structure of the T7SSb core unit (T7bCU) composed of YukB, YukC, and YukD from Bacillus subtilis, revealing how these components assemble within the secretion machinery.
www.science.org/doi/10.1126/...
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A ubiquitin-like protein controls assembly of a bacterial type VIIb secretion system
Cryo-EM structure reveals how a ubiquitin-like protein orchestrates assembly of a bacterial weapon system.
https://www.science.org/doi/10.1126/sciadv.ady9587
4
85
41
reposted by
James A. Letts
Science Magazine
3 months ago
Using an integrative phylogenomic approach, new research in Science reveals unprecedented phylogenomic support for sponges as the sister lineage to all other animals. Learn more in a new
#SciencePerspective
:
https://scim.ag/4r7SLqm
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Sponging away phylogenomic incongruence
Genes with strong and consistent signals favor sponges as humansβ most distant animal relatives
https://scim.ag/4r7SLqm
0
36
7
reposted by
James A. Letts
Charles University, Faculty of Science
3 months ago
β¨ A study in
nature.com
from our Faculty at
@unikarlova.cuni.cz
reveals Solarion arienae, a rare
#protist
forming a newly identified eukaryotic supersroup Disparia. A unique window into early
#eukaryotic
cell
#evolution
. ππ¬π
www.nature.com/articles/s41...
0
44
21
reposted by
James A. Letts
Nogales Lab
3 months ago
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...
1
59
21
reposted by
James A. Letts
Nature Microbiology
3 months ago
#NewResearch
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated C. difficile infection in mice.
#MicroSky
π¦ π
www.nature.com/articles/s41...
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Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin - Nature Microbiology
A bile acid-bound structure of toxin TcdB revealed the mechanism of inhibition and guided the design of a synthetic bile acid that alleviated Clostridioides difficile infection in mice.
https://www.nature.com/articles/s41564-025-02179-1?utm_source=bluesky&utm_medium=social&utm_campaign=nmicrobiol
0
36
19
reposted by
James A. Letts
3 months ago
Now in the journal issue! Molecular mechanism of activation of kainate receptor GluK2 in complex with auxiliary subunit Neto2.
www.nature.com/articles/s41...
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9
2
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