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James A. Letts

@lettsscience.bsky.social

123 followers 221 following 17 posts

James A. Letts @lettsscience.bsky.social · 09/02/2026

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...

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James A. Letts @lettsscience.bsky.social · 10/11/2025

We show that hydrophobic biguanides also inhibit complex I in a state dependent manner but their inhibition can be explained using a competitive framework. Whereas, due to the trapping mechanism induced by quinone there is positive cooperativity between the binding of metformin and quinone. 3/n

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James A. Letts @lettsscience.bsky.social · 10/11/2025

Our data are consistent with a state-dependent inhibitor trapping mechanism, in which the hydrophilic metformin can only bind to complex I in its "open" state and then gets trapped on the complex due to quinone-binding-induced closing of the active site, trapping metformin in the Q-tunnel. 2/n

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James A. Letts @lettsscience.bsky.social · 10/10/2025

Next, using the alphaproteobacterial CI structure and its shared subunits with all known eukaryotic structures we propose the structure of CI from the First Eukaryotic Common Ancestor (FECA). This indicates that eukaryotic CI gained a new subunit every ~10-30 million years between FECA and LECA.

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James A. Letts @lettsscience.bsky.social · 10/10/2025

By comparing the structures of mitochondrial complex I across eukaryotic species and mapping them our best current model of the eukaryotic tree of life (yellow stars below indicate clades with complex I structures) we propose the structure of complex I from the Last Eukaryotic Common Ancestor (LECA)

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James A. Letts @lettsscience.bsky.social · 10/10/2025

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

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