Evidence map›Paper›PMID 40631248›Full record

ArticlebioRxiv : the preprint server for biology2025

Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.

Eric Greene, Richard Muniz, Hiroki Yamamura, Samuel E Hoff, Priyanka Bajaj, D John Lee, Erin M Thompson, Angelika Arada, Gyun Min Lee, Massimiliano Bonomi and 2 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Eric GreeneDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.ORCID 0000-0003-1717-0914
Richard MunizDepartment of Biochemistry. University of Washington, Seattle WA.
Hiroki YamamuraDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.
Samuel E HoffInstitut Pasteur, Université Paris Cité, CNRS UMR 3528, Computational Structural Biology Unit, Paris, France.ORCID 0009-0006-8901-221X
Priyanka BajajDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.ORCID 0000-0001-8474-6149
D John LeeDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-5132-3243
Erin M ThompsonDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-6085-3051
Angelika AradaDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.
Gyun Min LeeDepartment of Biological Sciences, KAIST, Daejeon, 34141 Republic of Korea.
Massimiliano BonomiInstitut Pasteur, Université Paris Cité, CNRS UMR 3528, Computational Structural Biology Unit, Paris, France.ORCID 0000-0002-7321-0004
Justin M KollmanDepartment of Biochemistry. University of Washington, Seattle WA.ORCID 0000-0002-0350-5827
James S FraserDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.ORCID 0000-0002-5080-2859

Funding

The Stanford-SLAC CryoEM CenterR24GM154186 · NIGMS · STANFORD UNIVERSITY · PI Wah Chiu, BRITT HEDMAN · 2024 to 2026
$19.3M
Equipment for Discovering and Manipulating Macromolecular Conformational EnsemblesR35GM145238 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI James Solomon Fraser · 2022 to 2026
$3.1M
Structure and function of metabolic enzyme assembliesR35GM149542 · NIGMS · UNIVERSITY OF WASHINGTON · PI Justin M Kollman · 2023 to 2026
$2.2M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG opticsS10OD026881 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2019 to 2019
$1.8M
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
Connecting in vitro glutamine synthetase biophysics with the cellular environmentF32GM144982 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GREENE, ERIC RAYMOND · 2022 to 2023
$113k
NIGMS NIH HHS F32 GM144982NIGMS NIH HHS R24 GM154186NIGMS NIH HHS R35 GM145238NIGMS NIH HHS R35 GM149542NIH HHS S10 OD020054NIH HHS S10 OD021741NIH HHS S10 OD026881
6 · The paper itself

Abstract

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

Identifiers

PMID40631248
PMCPMC12236511

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.