James A. Letts
@lettsscience.bsky.social
Pinned
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 ...
www.nature.com
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...
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...
Reposted by James A. Letts
Genome sequencing technology is introducing biologists to a world of quasi-life forms that they’ve never met before. @jakebuehler.bsky.social reports: www.quantamagazine.org/a-cell-so-mi...
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.
www.quantamagazine.org
November 24, 2025 at 2:56 PM
Genome sequencing technology is introducing biologists to a world of quasi-life forms that they’ve never met before. @jakebuehler.bsky.social reports: www.quantamagazine.org/a-cell-so-mi...
Reposted by James A. Letts
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
Rare microbial relict sheds light on an ancient eukaryotic supergroup www.nature.com/articles/s41...
#Protists #Microbes #Evolution #Eukaryotes #TreeOfLife
November 23, 2025 at 5:11 PM
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
Rare microbial relict sheds light on an ancient eukaryotic supergroup www.nature.com/articles/s41...
#Protists #Microbes #Evolution #Eukaryotes #TreeOfLife
Reposted by James A. Letts
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...
www.nature.com/articles/s41...
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.
www.nature.com
November 21, 2025 at 9:30 AM
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...
www.nature.com/articles/s41...
Reposted by James A. Letts
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/...
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/...
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.
www.science.org
November 21, 2025 at 7:05 PM
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/...
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/...
Reposted by James A. Letts
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
Learn more in a new #SciencePerspective: https://scim.ag/4r7SLqm
Sponging away phylogenomic incongruence
Genes with strong and consistent signals favor sponges as humans’ most distant animal relatives
scim.ag
November 19, 2025 at 8:54 PM
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
Learn more in a new #SciencePerspective: https://scim.ag/4r7SLqm
Reposted by James A. Letts
✨ 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. 🌍🔬👏
www.nature.com/articles/s41...
www.nature.com/articles/s41...
November 19, 2025 at 4:03 PM
✨ 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. 🌍🔬👏
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by James A. Letts
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...
www.biorxiv.org/content/10.1...
November 18, 2025 at 10:43 PM
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...
www.biorxiv.org/content/10.1...
Reposted by James A. Letts
#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 🦠💊
www.nature.com/articles/s41...
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 🦠💊
www.nature.com/articles/s41...
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.
www.nature.com
November 18, 2025 at 2:07 PM
#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 🦠💊
www.nature.com/articles/s41...
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 🦠💊
www.nature.com/articles/s41...
Reposted by James A. Letts
Now in the journal issue! Molecular mechanism of activation of kainate receptor GluK2 in complex with auxiliary subunit Neto2.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
November 18, 2025 at 5:59 PM
Now in the journal issue! Molecular mechanism of activation of kainate receptor GluK2 in complex with auxiliary subunit Neto2.
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Reposted by James A. Letts
Prohibitins aren’t hanging out just anywhere in the membrane — they prefer the 💁♀️💎✨VIP section💅🪩🥂
Lab all-star @mmedina300kv.bsky.social maps these microdomains using cryo-ET + surface morphometrics.
s/o to #teamtomo #cryoET co-authors
@hamid13r.bsky.social
@attychang.bsky.social
@baradlab.com
Lab all-star @mmedina300kv.bsky.social maps these microdomains using cryo-ET + surface morphometrics.
s/o to #teamtomo #cryoET co-authors
@hamid13r.bsky.social
@attychang.bsky.social
@baradlab.com
Prohibitin complexes associate with unique membrane microdomains in cells https://www.biorxiv.org/content/10.1101/2025.11.14.688579v1
November 17, 2025 at 12:22 AM
Prohibitins aren’t hanging out just anywhere in the membrane — they prefer the 💁♀️💎✨VIP section💅🪩🥂
Lab all-star @mmedina300kv.bsky.social maps these microdomains using cryo-ET + surface morphometrics.
s/o to #teamtomo #cryoET co-authors
@hamid13r.bsky.social
@attychang.bsky.social
@baradlab.com
Lab all-star @mmedina300kv.bsky.social maps these microdomains using cryo-ET + surface morphometrics.
s/o to #teamtomo #cryoET co-authors
@hamid13r.bsky.social
@attychang.bsky.social
@baradlab.com
Reposted by James A. Letts
MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
November 14, 2025 at 6:38 PM
MISO: microfluidic protein isolation enables single-particle cryo-EM structure determination from a single cell colony.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
Or from a single dish of HEK cell culture in the case of two membrane proteins.
Out in Nature Methods now! lnkd.in/gpyBSceg
Wonderful collaboration with the Efremov lab.
Reposted by James A. Letts
November 13, 2025 at 7:23 PM
Reposted by James A. Letts
Very cool structures, congrats to all! #microsky
Link seemed broken though so here's a working one:
www.pnas.org/doi/10.1073/...
Link seemed broken though so here's a working one:
www.pnas.org/doi/10.1073/...
Pleased to see this collaboration with a great PhD student Pei Cing Ng, from Prof. Luning Liu's lab at Liverpool University published. Structure of the H. neapolitanus carbonic anhydrase and localisation in a mini-carboxysome: www.pnas.org/doi/epdf/10....
November 13, 2025 at 1:44 PM
Very cool structures, congrats to all! #microsky
Link seemed broken though so here's a working one:
www.pnas.org/doi/10.1073/...
Link seemed broken though so here's a working one:
www.pnas.org/doi/10.1073/...
Reposted by James A. Letts
Design stable, folded proteins using only the 10 "ancient" amino acids.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
October 31, 2025 at 7:40 PM
Design stable, folded proteins using only the 10 "ancient" amino acids.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Reposted by James A. Letts
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...
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...
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 ...
www.nature.com
November 10, 2025 at 6:35 PM
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...
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...
Reposted by James A. Letts
Getting Rosalind Franklin’s story right is crucial, because she has become a role model for women going into science
www.nature.com/articles/d41...
www.nature.com/articles/d41...
What Rosalind Franklin truly contributed to the discovery of DNA’s structure
Franklin was no victim in how the DNA double helix was solved. An overlooked letter and an unpublished news article, both written in 1953, reveal that she was an equal player.
www.nature.com
November 10, 2025 at 9:44 AM
Getting Rosalind Franklin’s story right is crucial, because she has become a role model for women going into science
www.nature.com/articles/d41...
www.nature.com/articles/d41...
Reposted by James A. Letts
New work from Tahirov x Lim collaboration! @qixianghe.bsky.social from my lab contributed the cryo-EM structures for this work. We are excited to help explain how anti-HSV drugs work and to guide their future development.
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir
Structural studies of HSV-1 helicase-primase revealed how pritelivir and amenamevir bind and block its helicase activity.
www.science.org
November 10, 2025 at 12:14 AM
New work from Tahirov x Lim collaboration! @qixianghe.bsky.social from my lab contributed the cryo-EM structures for this work. We are excited to help explain how anti-HSV drugs work and to guide their future development.
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
www.science.org/doi/10.1126/...
@unmc.bsky.social @uwbiochem.bsky.social
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...
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...
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 ...
www.nature.com
November 10, 2025 at 6:35 PM
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...
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...
Reposted by James A. Letts
CryoSift is now out @actacrystf.iucr.org doi.org/10.1107/S205... Thanks to all involved. Happy processing!
November 7, 2025 at 4:58 PM
CryoSift is now out @actacrystf.iucr.org doi.org/10.1107/S205... Thanks to all involved. Happy processing!
Reposted by James A. Letts
An Asgard archaeon with internal membrane compartments
Brilliant study led by @fmacleod.bsky.social and Andriko von Kügelgen. Tight collaboration with @buzzbaum.bsky.social and lab. Congrats to all authors!
www.biorxiv.org/content/10.1...
Brilliant study led by @fmacleod.bsky.social and Andriko von Kügelgen. Tight collaboration with @buzzbaum.bsky.social and lab. Congrats to all authors!
www.biorxiv.org/content/10.1...
November 7, 2025 at 10:44 AM
An Asgard archaeon with internal membrane compartments
Brilliant study led by @fmacleod.bsky.social and Andriko von Kügelgen. Tight collaboration with @buzzbaum.bsky.social and lab. Congrats to all authors!
www.biorxiv.org/content/10.1...
Brilliant study led by @fmacleod.bsky.social and Andriko von Kügelgen. Tight collaboration with @buzzbaum.bsky.social and lab. Congrats to all authors!
www.biorxiv.org/content/10.1...
Reposted by James A. Letts
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...
November 5, 2025 at 4:23 PM
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...
Reposted by James A. Letts
Our paper in Science is out! @souravagrawal.bsky.social, @rlynn.bsky.social, @susvirkar.bsky.social, and the rest of the team show human RPA is a telomerase processivity factor essential for telomere maintenance. This reshapes our thinking about telomerase regulation. www.science.org/doi/10.1126/...
Human RPA is an essential telomerase processivity factor for maintaining telomeres
Telomerase counteracts telomere shortening by repeatedly adding DNA repeats to chromosome ends. We identified the replication protein A (RPA) heterotrimer as a telomerase processivity factor critical ...
www.science.org
October 30, 2025 at 10:07 PM
Our paper in Science is out! @souravagrawal.bsky.social, @rlynn.bsky.social, @susvirkar.bsky.social, and the rest of the team show human RPA is a telomerase processivity factor essential for telomere maintenance. This reshapes our thinking about telomerase regulation. www.science.org/doi/10.1126/...
Reposted by James A. Letts
🧬 Registration is open for the Phylogenomics Workshop in Český Krumlov!
Fantastic training opportunity for anyone working with genomic data and evolutionary questions.
Highly recommended - amazing course, great community, and a fantastic setting!
Fantastic training opportunity for anyone working with genomic data and evolutionary questions.
Highly recommended - amazing course, great community, and a fantastic setting!
October 30, 2025 at 4:41 PM
🧬 Registration is open for the Phylogenomics Workshop in Český Krumlov!
Fantastic training opportunity for anyone working with genomic data and evolutionary questions.
Highly recommended - amazing course, great community, and a fantastic setting!
Fantastic training opportunity for anyone working with genomic data and evolutionary questions.
Highly recommended - amazing course, great community, and a fantastic setting!
Reposted by James A. Letts
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
@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
October 30, 2025 at 3:21 AM
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
@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
Reposted by James A. Letts
In @nature.com: Using AI and other cutting-edge techniques, the Klinge lab has captured the first near-continuous "molecular movie" of ribosome formation—revealing, frame by frame, how cells build the protein factories that make life possible.
More here: https://bit.ly/3LbHTaF
More here: https://bit.ly/3LbHTaF
October 29, 2025 at 5:22 PM
In @nature.com: Using AI and other cutting-edge techniques, the Klinge lab has captured the first near-continuous "molecular movie" of ribosome formation—revealing, frame by frame, how cells build the protein factories that make life possible.
More here: https://bit.ly/3LbHTaF
More here: https://bit.ly/3LbHTaF