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
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
Reposted by James A. Letts
Please RT. Post-doc opportunity alert! 💥 closing 10th December.. Come join our team (www.thelowlab.org) at Imperial, London, working on the structure and mechanism of bacterial secretion systems.
For more details and to apply please see
www.imperial.ac.uk/jobs/search-...
For more details and to apply please see
www.imperial.ac.uk/jobs/search-...
October 29, 2025 at 5:11 PM
Please RT. Post-doc opportunity alert! 💥 closing 10th December.. Come join our team (www.thelowlab.org) at Imperial, London, working on the structure and mechanism of bacterial secretion systems.
For more details and to apply please see
www.imperial.ac.uk/jobs/search-...
For more details and to apply please see
www.imperial.ac.uk/jobs/search-...
Reposted by James A. Letts
Nature research paper: Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites
go.nature.com/47qdigV
go.nature.com/47qdigV
Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites - Nature
A recombinant antivenom composed of eight nanobodies provides broad protection against venom-induced lethality and dermonecrosis in mice challenged with venoms from cobras, mambas and rinkhals snakes.
go.nature.com
October 29, 2025 at 6:30 PM
Nature research paper: Nanobody-based recombinant antivenom for cobra, mamba and rinkhals bites
go.nature.com/47qdigV
go.nature.com/47qdigV
Reposted by James A. Letts
Thrilled to see Leyre’s PhD work finally out!
We reported the #cryoEM structures of an extracellular contractile injection system from P. luminescens in extended and contracted states, providing structural insight into its architecture and contraction mechanism 🔬
www.nature.com/articles/s41...
We reported the #cryoEM structures of an extracellular contractile injection system from P. luminescens in extended and contracted states, providing structural insight into its architecture and contraction mechanism 🔬
www.nature.com/articles/s41...
Structural characterization of an extracellular contractile injection system from Photorhabdus luminescens in extended and contracted states - Nature Communications
Marín-Arraiza and colleagues report the cryo-EM structures of an extracellular contractile injection system from Photorhabdus luminescens in extended and contracted states, providing structural insigh...
www.nature.com
October 22, 2025 at 1:25 PM
Thrilled to see Leyre’s PhD work finally out!
We reported the #cryoEM structures of an extracellular contractile injection system from P. luminescens in extended and contracted states, providing structural insight into its architecture and contraction mechanism 🔬
www.nature.com/articles/s41...
We reported the #cryoEM structures of an extracellular contractile injection system from P. luminescens in extended and contracted states, providing structural insight into its architecture and contraction mechanism 🔬
www.nature.com/articles/s41...
Reposted by James A. Letts
Chris Russo and Anastasiia Gusach have developed a new method to prepare #cryoEM samples that avoids protein damage during freezing
Read more: www2.mrc-lmb.cam.ac.uk/a-new-method...
#LMBResearch
Read more: www2.mrc-lmb.cam.ac.uk/a-new-method...
#LMBResearch
October 22, 2025 at 4:41 PM
Chris Russo and Anastasiia Gusach have developed a new method to prepare #cryoEM samples that avoids protein damage during freezing
Read more: www2.mrc-lmb.cam.ac.uk/a-new-method...
#LMBResearch
Read more: www2.mrc-lmb.cam.ac.uk/a-new-method...
#LMBResearch
Reposted by James A. Letts
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
A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
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...
rdcu.be
October 20, 2025 at 12:55 PM
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
A team effort led by @mehsehret.bsky.social & Anurag Shukla @akhilvaidya.bsky.social! #cryoEM #malaria
Reposted by James A. Letts
Structures of rotary ATP synthase from Thermus thermophilus during proton powered ATP synthesis | Science Advances www.science.org/doi/10.1126/...
Structures of rotary ATP synthase from Thermus thermophilus during proton powered ATP synthesis
Cryo-EM snapshots of the ATP synthase driven by proton motive force reveal the torsional deformation during ATP synthesis.
www.science.org
October 18, 2025 at 7:42 PM
Structures of rotary ATP synthase from Thermus thermophilus during proton powered ATP synthesis | Science Advances www.science.org/doi/10.1126/...
Reposted by James A. Letts
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/...
www.science.org/doi/10.1126/...
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...
www.science.org
October 16, 2025 at 7:17 PM
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/...
www.science.org/doi/10.1126/...
Reposted by James A. Letts
ISTA @istaresearch.bsky.social is hiring a tenure-track staff scientist in Computational Structural Biology, to develop tools for cryo-EM, cryo-ET, structural prediction methods and protein interaction analysis!
Please spread the word!
ista.ac.at/en/job/tenur...
Please spread the word!
ista.ac.at/en/job/tenur...
Tenure-based Research Staff Scientist Position in Computational Structural Biology
ISTA (www.ista.ac.at) is seeking a highly skilled Staff Scientist in Computational Structural Biology to support and advance the Institute’s structural biology research through the development and imp...
ista.ac.at
October 15, 2025 at 2:08 PM
ISTA @istaresearch.bsky.social is hiring a tenure-track staff scientist in Computational Structural Biology, to develop tools for cryo-EM, cryo-ET, structural prediction methods and protein interaction analysis!
Please spread the word!
ista.ac.at/en/job/tenur...
Please spread the word!
ista.ac.at/en/job/tenur...
Reposted by James A. Letts
Have you ever looked at the night sky and wondered if there’s a chlorophyll f in the reaction centre of Photosystem I from far-red light adapted cyanobacteria? 🦠
Well, we did (don’t judge) and the work that followed is now out as a First Release in @science.org
www.science.org/doi/10.1126/...
Well, we did (don’t judge) and the work that followed is now out as a First Release in @science.org
www.science.org/doi/10.1126/...
Locating the missing chlorophylls f in far-red photosystem I
The discovery of chlorophyll f-containing photosystems, with their long-wavelength photochemistry, represented a distinct, low-energy paradigm for oxygenic photosynthesis. Structural studies on chloro...
www.science.org
October 11, 2025 at 10:37 AM
Have you ever looked at the night sky and wondered if there’s a chlorophyll f in the reaction centre of Photosystem I from far-red light adapted cyanobacteria? 🦠
Well, we did (don’t judge) and the work that followed is now out as a First Release in @science.org
www.science.org/doi/10.1126/...
Well, we did (don’t judge) and the work that followed is now out as a First Release in @science.org
www.science.org/doi/10.1126/...
Reposted by James A. Letts
Pretty excited to share our new preprint!
Non-photosynthetic Plastid Replacement by a Primary Plastid in the Making
www.biorxiv.org/content/10.1...
Non-photosynthetic Plastid Replacement by a Primary Plastid in the Making
www.biorxiv.org/content/10.1...
October 10, 2025 at 3:34 AM
Pretty excited to share our new preprint!
Non-photosynthetic Plastid Replacement by a Primary Plastid in the Making
www.biorxiv.org/content/10.1...
Non-photosynthetic Plastid Replacement by a Primary Plastid in the Making
www.biorxiv.org/content/10.1...
New Review from the lab:
Respiratory complex I (CI) is composed of a conserved set of core subunits and additional accessory subunits that vary depending on the organism. Here, we categorize CI subunits from available structures to map the evolution of CI across eukaryotes. 1/n
tinyurl.com/txtrbfnw
Respiratory complex I (CI) is composed of a conserved set of core subunits and additional accessory subunits that vary depending on the organism. Here, we categorize CI subunits from available structures to map the evolution of CI across eukaryotes. 1/n
tinyurl.com/txtrbfnw
October 10, 2025 at 4:11 PM
New Review from the lab:
Respiratory complex I (CI) is composed of a conserved set of core subunits and additional accessory subunits that vary depending on the organism. Here, we categorize CI subunits from available structures to map the evolution of CI across eukaryotes. 1/n
tinyurl.com/txtrbfnw
Respiratory complex I (CI) is composed of a conserved set of core subunits and additional accessory subunits that vary depending on the organism. Here, we categorize CI subunits from available structures to map the evolution of CI across eukaryotes. 1/n
tinyurl.com/txtrbfnw
Reposted by James A. Letts
Mitochondrial diseases have seemed intractable, but last month the Food and Drug Administration OK’d the first treatment targeting a mitochondrial flaw. https://scim.ag/4q3Ymxz
First approved drug for mitochondrial disease could pave way for more treatments
Researchers are testing multiple treatments for the rare genetic conditions
scim.ag
October 9, 2025 at 8:47 PM
Mitochondrial diseases have seemed intractable, but last month the Food and Drug Administration OK’d the first treatment targeting a mitochondrial flaw. https://scim.ag/4q3Ymxz
Reposted by James A. Letts
Structure of Photosystem I-FCP from giant kelp uncovers drivers of antenna evolution across the red lineage https://www.biorxiv.org/content/10.1101/2025.10.07.680316v1
October 8, 2025 at 1:45 AM
Structure of Photosystem I-FCP from giant kelp uncovers drivers of antenna evolution across the red lineage https://www.biorxiv.org/content/10.1101/2025.10.07.680316v1