Publications
Understand how protein motions contribute to enzyme catalysis, regulation, and protein turnover for large enzyme complexes by combining cryoEM with enzymology techniques
Special thanks to our collaborators on this project the Kollman lab at UW and @bonomimax.bsky.social for their tremendous contributions and insight. Keep an eye out for future work on GS regulatory mechanisms here!
www.egreenelab.org/publications/
09.07.2025 18:33 — 👍 1 🔁 0 💬 0 📌 0
Using #cryoEM with MD ensemble refinements, biochemical interrogation, and cellular assays, we propose that human glutamine synthetase (GS) is subject to product based feedback inhibition via an allosteric, filament formation mechanism.
09.07.2025 18:33 — 👍 1 🔁 0 💬 1 📌 0
Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity
To maintain metabolic homeostasis, enzymes must adapt to fluctuating nutrient levels through mechanisms beyond gene expression. Here, we demonstrate that human glutamine synthetase (GS) can reversibly polymerize into filaments aided by a composite binding site formed at the filament interface by the product, glutamine. Time-resolved cryo-electron microscopy (cryo-EM) confirms that glutamine binding stabilizes these filaments, which in turn exhibit reduced catalytic specificity for ammonia at physiological concentrations. This inhibition appears induced by a conformational change that remodulates the active site loop ensemble gating substrate entry. Metadynamics ensemble refinement revealed >10 Å conformational range for the active site loop and that the loop is stabilized by transient contacts. This disorder is significant, as we show that the transient contacts which stabilize this loop in a closed conformation are essential for catalysis both in vitro and in cells. We propose that GS filament formation constitutes a negative-feedback mechanism, directly linking product concentration to the structural and functional remodeling of the enzyme. ### Competing Interest Statement HY is an employee of JSR. J.S.F. is a consultant to, a shareholder of, and receives sponsored research support from Relay Therapeutics. National Institutes of Health, https://ror.org/01cwqze88, F32GM144982, R35GM145238
❄️ Even high-resolution #cryoEM maps can still hide a few secrets 🔍 Discover how we uncover them in this exciting collaboration with @egreene.bsky.social @fraserlab.com @pasteur.fr @cnrsbiologie.bsky.social
📄 Preprint: www.biorxiv.org/content/10.1...
07.07.2025 15:20 — 👍 20 🔁 6 💬 0 📌 0
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Sharing the good and the bad of electron microscopy and related ❄️🔬Ice crystal hall of fame 🧊🏆 #ElectronMicroscopy #CryoEM #TeamTomo
Principal Investigator - Tata Memorial Centre - ACTREC, Mumbai, India
Developmental Biology & Disease mechanisms!
Facts & strategy, in an authoritarian takeover.
Rightwing billionaires want to privatize NIH and use it to control universities.
We work to cure diseases like cancer.
Pers views. #science #medicine
SFSU Masters Biochemistry Student working in Eric Greene’s lab. UC Berkeley MCB: Biochemistry Undergraduate degree. Former American Slovenian Educational Foundation Fellow. Passionate about cancer research.
Structural Biology to the rescue. Postdoc with Gabriel Lander at Scripps Research. PhD with Arne Moeller. #cryoEM ❄️🔬 🎹⛳
Doing science @UCSF in the Coyote-Maestas and Manglik Labs. Former Jackrel Lab @WUSTL www.matthewkhoward.com
Structural Biology, Protein Engineering
Biochemistry & Molecular Biology PhD
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Postdoc at The Rockefeller University
Multi-disciplinary early discovery researcher | Biotech Target Selection, Hit Discovery Strategy, Protein Engineering, Structure-Based Drug Design | Formerly at UCSF, MIT-WIBR, Relay Tx
Professor, Georgia Tech Chemistry and Biochemistry. Georgia Research Alliance Eminent Scholar. Senior Editor, Protein Science. American, British, Swedish, Kurdish. Pianist, photographer, foodie, dreamer, mom. She/they. #FirstGen #MENA All views my own
News from the Sternberg lab at Columbia University, Howard Hughes Medical Institute.
Posts are from lab members and not Samuel Sternberg unless signed SHS. Posts represent personal views only.
Visit us at www.sternberglab.org
Chemical biologist. Protein editing. Dog mom and nature enthusiast.
Molecular Biologist (aemonten.github.io) 丨Chief Editor @ CSH Protocols (cshprotocols.cshlp.org) 丨Head of the Integrity in Publishing Group at CSHL Press 丨Chair "Molecular Biosystems Conference" (molbiosystems.com) 丨(Oxford) Comma King 丨Central Dogma Police
Chemical biologist at MIT, passionate about glycoscience and all chemical biology
Chemical biologist at Stanford with a love for covalent binding molecules and hydrolases.
Genome editing, functional genomics, and cells figuring out how to eat themselves without dying. Professor of Genome Biology at ETH Zürich.
Scientist. Christ-follower. Prof @UPenn. Director of Folding@home. Legaly blind. Father.
scientist. shipman lab at gladstone | UCSF.
