Biochemistry

Common and distinct roles of AMPKγ isoforms in small-molecule activator-stimulated glucose uptake in mouse skeletal muscle

1. Dipsikha Biswas
2. Ever Espino-Gonzalez
3. Danial Ahwazi
4. Jordana B. Freemantle
5. Charline Jomard
6. Jonas Brorson
7. Agnete N. Schou
8. Jean Farup
9. Julien Gondin
10. Jesper Just
11. Marc Foretz
12. Jonas T. Treebak
13. Marianne Agerholm
14. Kei Sakamoto

Reviewed by PREreview

Cryo-EM reveals multiple mechanisms of ribosome inhibition by doxycycline

1. William S. Stuart
2. Michail N. Isupov
3. Mathew McLaren
4. Christopher H. Jenkins
5. Adam Monier
6. Bertram Daum
7. Isobel H. Norville
8. Vicki A.M. Gold
9. Nicholas J. Harmer

Reviewed by preLights

A sulfatide-centered ultra-high resolution magnetic resonance MALDI imaging benchmark dataset for MS1-based lipid annotation tools

1. Lars Gruber
2. Stefan Schmidt
3. Thomas Enzlein
4. Carsten Hopf

Reviewed by GigaScience

Shifting the PPARγ conformational ensemble towards a transcriptionally repressive state improves covalent inhibitor efficacy

1. Liudmyla Arifova
2. Brian S MacTavish
3. Zane Laughlin
4. Mithun Nag Karadi Giridhar
5. Jinsai Shang
6. Min-Hsuan Li
7. Xiaoyu Yu
8. Di Zhu
9. Theodore M Kamenecka
10. Douglas J Kojetin

• Curated by eLife

  eLife Assessment

  This manuscript presents a fundamental advance in our understanding of nuclear receptor pharmacology by expanding on previous work demonstrating dual ligand occupancy in the peroxisome proliferator-activated receptor-gamma (PPARγ). Using a compelling combination of biophysical, biochemical, and cellular approaches, the authors show that covalent inverse agonists with enhanced efficacy shift the receptor conformation toward a transcriptionally repressive state that limits orthosteric ligand co-binding more effectively. This revised manuscript further strengthens support for a proximal, bidirectional allosteric model of dual ligand occupancy by sharpening the distinction between prior and new findings, adding clear conceptual figures, and strengthening statistical rigor.

Reviewed by eLife

RemoteFoldSet: Benchmarking Structural Awareness of Protein Language Models

1. Zinnia Ma
2. Neville P. Bethel

Reviewed by Arcadia Science

A high-resolution analysis of arrestin2 interactions responsible for CCR5 endocytosis

1. Ivana Petrovic
2. Samit Desai
3. Polina Isaikina
4. Layara Akemi Abiko
5. Anne Spang
6. Stephan Grzesiek

• Curated by eLife

  eLife Assessment

  The authors investigate arrestin2-mediated CCR5 endocytosis in the context of clathrin and AP2 contributions. Using an extensive set of NMR experiments, and supported by microscopy and other biophysical assays, the authors provide compelling data on the roles of AP2 and clathrin in CCR5 endocytosis. This important work will appeal to an audience beyond those studying chemokine receptors, including those studying GPCR regulation and trafficking. The distinct role of AP2 and not clathrin will be of particular interest to those studying GPCR internalization mechanisms.

Reviewed by eLife

Mitochondrial Fatty Acid Oxidation is Stimulated by Red Light Irradiation

1. Manuel Alejandro Herrera
2. Camille C. Caldeira da Silva
3. Mauricio S. Baptista
4. Alicia J. Kowaltowski

Reviewed by preLights

Identification of the Regulatory Elements and Protein Substrates of Lysine Acetoacetylation

1. Qianyun Fu
2. Terry Nguyen
3. Bhoj Kumar
4. Parastoo Azadi
5. Y George Zheng

• Curated by eLife

  eLife Assessment

  This useful study reports a method to detect and analyze a novel post-translational modification, lysine acetoacetylation (Kacac), finding it regulates protein metabolism pathways. The study unveils epigenetic modifiers involved in placing this mark, including key histone acetyltransferases such as p300, and concomitant HDACs, which remove the mark. Proteomic and bioinformatics analysis identified many human proteins with Kacac sites, potentially suggesting broad effects on cellular processes and disease mechanisms. The data presented are solid and the study will be of interest to those studying protein and metabolic regulation.

Reviewed by eLife

A simplified and highly efficient cell-free protein synthesis system for prokaryotes

1. Xianshengjie Lang
2. Changbin Zhang
3. Jingxuan Lin
4. Zhe Zhang
5. Wenfei Li

• Curated by eLife

  eLife Assessment

  The study presents valuable findings of an optimized E. coli cell-free protein synthesis (eCFPS) system that has been simplified by reducing the number of core components from 35 to 7; furthermore, the findings communicate a simplified 'fast lysate' preparation that eliminates the need for traditional runoff and dialysis steps. This study is an advance towards simplifying protein expression workflows, and the evidence provided is solid, starting with nanoluc, a protein that expresses readily in many systems, to applications to more challenging proteins like the functional self-assembling vimentin and the active restriction endonuclease Bsal. Data on the underlying mechanisms and efficiency of the presented system in terms of protein yield relative to other known cell-free systems would greatly enhance the findings' significance and the strength of the evidence. The paper remains of interest to scientists in microbiology, biotechnology and protein synthesis.

Reviewed by eLife

Cryo-EM structure of the bicarbonate receptor GPR30

1. Shota Kaneda
2. Airi Jo-Watanabe
3. Hiroaki Akasaka
4. Hidetaka S Oshima
5. Takehiko Yokomizo
6. Wataru Shihoya
7. Osamu Nureki

• Curated by eLife

  eLife Assessment

  This study resolves a cryo-EM structure of the GPCR, human GPR30, which responds to bicarbonate and regulates cellular responses to pH and ion homeostasis. Understanding the ligand and the mechanism of activation is important to the field of receptor signaling and potentially facilitates drug development targeting this receptor. Structures and functional assays provide solid evidence for a potential bicarbonate binding site.

Reviewed by eLife