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New paper alert 🚨 from @cgemcci.bsky.social showing high-resolution cryo-EM structures and mass spectrometry data that help us understand how beta-hydroxy acids are accommodated and incorporated by the ribosome!

In the latest installment of @asbmb.bsky.social 's career exploration podcast, "In conversation with..." Lou Stancato, VP of Enabling Technologies at the Indiana Biosciences Research Institute shares insights from his career: www.asbmb.org/career-resou...

Check out our latest preprint describing two structures of ribosomes complexed with the two enantiomers of a β2-hydroxy acid. Our structures show that despite stereochemical differences, both are ultimately well positioned for bond formation within the ribosome! chemrxiv.org/engage/chemr...

Check out the latest episodes of the #ASBMB podcast Cindy Khuu shares her story of pursuing a career in regulatory affairs Nisha Cavanaugh, talks about her role in research administration Shyretha Brown, shares her experience as the director of a non-profit! www.asbmb.org/career-resou...

Engaging discussions with biological and life sciences professionals about their career journeys and the various opportunities available to graduate students and postdocs.

The ribosomal incorporation of backbone-modified amino acid analogs into peptides and proteins enables the programmed synthesis of sequence-defined biopolymers with tunable properties. However, the su...

Engaging discussions with biological and life sciences professionals about their career journeys and the various opportunities available to graduate students and postdocs.

C-GEM's work was highlighted by APS! americanpeptidesociety.org/research/rib... Congrats to @c-majumdar.bsky.social, @alexandra-kent.bsky.social, @nxhamlish.bsky.social, Cathy, Katie, @jhdcate.bsky.social, and Alanna! Read the original paper in JACS: pubs.acs.org/doi/10.1021/... #NSFfunded

"Use it or lose it." This is great advice for exercise, but when cells need to slow down or go dormant, they need to store ribosomes to recover growth in the future. They use hibernation factors to do this. Here is our latest story on how archaea hibernate ribosomes (1/7): doi.org/10.64898/202...

Jennifer Doudna @jenniferdoudna.bsky.social @doudna-lab.bsky.social speaks with Cleo Abrams on the history and future of #CRISPR 🧬. Watch here: youtu.be/0OXaanDHENI?...

Researchers in the Cate and Schepartz Groups at the University of California, Berkeley, and the Lawrence Berkeley National Laboratory, published in the <em>Journal of the American Chemical Society</em...

americanpeptidesociety.org

A back-to-back paper from Alanna Schepartz and @jhdcate.bsky.social groups shows how the E. coli ribosome supports the incorporation of the non-α-amino acid monomers! pubs.acs.org/doi/10.1021/...

Final grad paper is officially out! Grateful for the incredible team and all the support along the way! www.nature.com/articles/s41...

C-GEM, the NSF Center for Genetically Encoded Materials

YouTube video by Cleo Abram

Engineering the translation apparatus to accept backbone-modified amino acid analogues would enable the programmed synthesis of sequence-defined biopolymers with tunable properties. β-Hydroxy acids ar...

Many flaviviruses generate specialized non-coding RNAs that resist degradation by host exonucleases, promoting viral infection. Here, the authors characterize an RNA element in Powassan virus, highlig...

Check out our new paper using mass spectrometry and cryo-EM to show ribosomal incorporation and accommodation of β-hydroxy acid stereoisomers, bringing us closer to ribosomal synthesis of non-natural polymers. @c-majumdar.bsky.social @jhdcate.bsky.social pubs.acs.org/doi/10.1021/...

Innovative Genomics Institute

Chintan's work demonstrating the efficient incorporation of non-α-amino acid backbones into proteins expressed in both E. coli and mammalian cells just came out! A great collaborative effort from @cgemcci.bsky.social! pubs.acs.org/doi/10.1021/...

Expanding the genetic code of living cells with noncanonical monomers (ncMs) relies on engineered aminoacyl-tRNA synthetases (aaRS) and their cognate tRNAs. Conventional aaRS engineering strategies rely on translation-dependent selection systems, limiting their utility for ncMs that are poorly accommodated by the native translational machinery. To address this limitation, we recently developed START, a translation-independent platform that selects Methanomethylophilus alvus pyrrolysyl-synthetase (MaPylRS) mutants based on their ability to acylate cognate tRNAMaPyl. START uses barcoded tRNAs to encode the identity of distinct aaRS mutants in a library. Acylation by active aaRS mutants protects the corresponding tRNAs from periodate oxidation, and their identity is retrieved subsequently through sequencing. START was previously applied to genetically encode noncanonical α-amino acids. Here, we successfully applied START to engineer MaPylRS mutants capable of acylating tRNAMaPyl with diverse non-α-amino acid substrates with good efficiency and fidelity, including (R) and (S) enantiomers of a β2-hydroxy acid, a β2-amino acids, and a malonate. Several mutants exhibit notable polyspecificity across noncanonical backbones while maintaining selectivity against their α-amino acid counterparts. Using these novel enzymes, we demonstrate the ribosomal incorporation of both (R)- and (S)-β2-hydroxy acids into a luciferase reporter protein expressed in Escherichia coli with good efficiency and fidelity. These results imply that highly active engineered aaRS/tRNA pairs can overcome the recently established limitations of EF-Tu with respect to non-α-amino acid substrates. The engineered MaPylRS mutants also enabled the successful incorporation of both (R)- and (S)-β2-hydroxy acids into a protein expressed in mammalian cells, demonstrating for the first time that eukaryotic translation can accommodate non-α-backbones.