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Bil Clemons

@profbilc.bsky.social

Hanisch Memorial Professor of Biochemistry at Caltech Program Officer in Science at CZI

Bil Clemons @profbilc.bsky.social · 13/07/2026

Huge congratulations to Juliet Lee and the whole team, and to our collaborators in the Sello lab at UCSF and the Denic lab at Harvard.

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Bil Clemons @profbilc.bsky.social · 13/07/2026

These structures finally explain more than a decade of structure-activity data generated across many labs without knowing the target — and point to a broader strategy: stabilizing transient protein complexes as a therapeutic approach.

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Bil Clemons @profbilc.bsky.social · 13/07/2026

Using cryo-EM, we found Retro compounds bind a cryptic pocket in Get3 and act as allosteric modulators — not blocking an enzyme or an interface, but trapping Get3 in a stalled complex with its co-chaperones Get4 and Bag6. The machinery locks up before it can hand off its cargo.

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Bil Clemons @profbilc.bsky.social · 13/07/2026

We now show both converge on one target: Get3, the ATPase chaperone at the heart of the GET pathway that delivers tail-anchored proteins to the ER.

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Bil Clemons @profbilc.bsky.social · 13/07/2026

Retro-1 and Retro-2 are two structurally unrelated small molecules that protect cells against a striking range of threats — ricin and Shiga toxins, coronaviruses, herpes- and polyomaviruses, and parasites like Leishmania and Chlamydia. 15 years after discovery, how they work has been contested.

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Bil Clemons @profbilc.bsky.social · 13/07/2026

I'm excited to announce a new preprint from the lab just posted to bioRxiv: “Retrograde trafficking inhibitors allosterically trap Get3 to block tail-anchored protein biogenesis.” www.biorxiv.org/content/10.6...

The structure of Human Get3 with the inhibitor Retro-2 bound in complex with Get4.

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Reposted by Bil Clemons

Biohub @biohub.org · 25/02/2026

🧵Antibiotic resistance is a public health crisis. But viruses called phages have been solving this problem for millennia. New research in @nature.com reveals how 3 different phages attack the same weak spot—a protein called MurJt—potentially leading to a new class of antibiotics.

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Reposted by Bil Clemons

jacob-kirsh.bsky.social @jacob-kirsh.bsky.social · 10/01/2026

Second, from the Clemons lab at Caltech, we determined high-resolution cryo-EM reconstructions for human and bacterial phosphoglycosyltransferase orthologs with a common inhibitor. www.biorxiv.org/content/10.6...

biorxiv.org

Structures of bacterial and human phosphoglycosyltransferases bound to a common inhibitor inform selective therapeutics

Glycoconjugates facilitate myriad biological processes, including cell–cell recognition and immune response, and they are generated by enzymes that transfer glycans. The orthologs MraY and DPAGT1 are ...

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Bil Clemons @profbilc.bsky.social · 25/03/2025

A new paper from our lab is available at doi.org/10.1101/2025.... The work describes how ArsA, which is involved in arsenic detoxification, utilizes nucleotides to drive dramatic conformational changes—multiple EM structures of a 64kDa protein. Congratulations to Shivansh Mahajan.

doi.org

Nucleotide and metalloid-driven conformational changes in the arsenite efflux ATPase ArsA

A common mechanism of arsenic detoxification in bacteria is arsenite (AsIII) efflux facilitated by the ArsAB pump that couples metalloid transport to ATP hydrolysis. The cytoplasmic ATPase component, ...

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Bil Clemons @profbilc.bsky.social · 20/03/2025

It was a pleasure for us. Thanks for making the effort and sharing your exciting work.

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Bil Clemons @profbilc.bsky.social · 18/12/2024

That’s a fun crowd.

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Bil Clemons @profbilc.bsky.social · 05/12/2024

It was a fun day. Thanks everyone!

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Reposted by Bil Clemons

Anirban Banerjee @banirbn.bsky.social · 05/12/2024

A privilege to host Bil Clemons @profbilc.bsky.social at the NIH Intramural Program for the Wednesday Afternoon Lecture Series. A fantastic talk about how phages use proteins to target bacterial cell wall biosynthesis machinery and a truly insightful lesson about inequity in science and society.

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