Biochemistry

Multiple modes of cholesterol translocation in the human Smoothened receptor

1. Prateek D Bansal
2. Maia Kinnebrew
3. Rajat Rohatgi
4. Diwakar Shukla

• Curated by eLife

  eLife Assessment

  In this important study, the authors conducted extensive sets of computational and investigations of the mechanism of cholesterol transport in the smoothened (SMO) protein. The computational component integrated multiple state-of-the-art approaches such as adaptive sampling, free energy simulations, and Markov state modeling, providing compelling support for the proposed mechanistic model, which is further validated with solid experimental mutagenesis data.

Reviewed by eLife

Systematic characterisation of site-specific proline hydroxylation using hydrophilic interaction chromatography and mass spectrometry

1. Hao Jiang
2. Jimena Druker
3. James W Wilson
4. Dalila Bensaddek
5. Jason R Swedlow
6. Sonia Rocha
7. Angus I Lamond

• Curated by eLife

  eLife Assessment

  The study presents a valuable resource of proline hydroxylation proteins for molecular biology studies in oxygen-sensing and cell signaling with the characterization of Repo-man proline hydroxylation site. The evidence supporting the claim of the authors is solid, although further clarification of the overall efficiency of the HILIC analysis, the specificity/sensitivity of immonium ion analysis, as well as quantification of proline hydroxylation identifications will be helpful. The work will be of interest to researchers studying post-translational modification, oxygen sensing, and cell signaling.

Reviewed by eLife

Determining the off-target activity of antibiotics and novel translation initiation sites in mitochondria

1. James Marks
2. Emma Young
3. Markus Hafner

• Curated by eLife

  eLife Assessment

  This valuable study presents findings on how prokaryotic antibiotics affect translation in mitochondrial ribosomes. Using mitoribosome profiling, the authors provide solid evidence that most tested antibiotics act similarly on bacterial and mitochondrial translation. Additionally, this work shows that alternative translation initiation events might exist in two specific mt-mRNAs (MT-ND1 and MT-ND5). However, additional biochemical and structural experiments are needed to support these findings.

Reviewed by eLife

Automated genome mining predicts structural diversity and taxonomic distribution of peptide metallophores across bacteria

1. Zachary L Reitz
2. Bita Pourmohsenin
3. Melanie Susman
4. Emil Thomsen
5. Daniel Roth
6. Alison Butler
7. Nadine Ziemert
8. Marnix H Medema

• Curated by eLife

  eLife Assessment

  This important and compelling study establishes a robust computational and experimental framework for the large-scale identification of metallophore biosynthetic clusters. The work advances beyond current standards, providing theoretical and practical value across microbiology, bioinformatics, and evolutionary biology.

Reviewed by eLife

Structure of the human CTF18−RFC clamp loader bound to PCNA

1. Giuseppina R Briola
2. Mohammad Tehseen
3. Amani Al-Amodi
4. Grace Young
5. Ammar U Danazumi
6. Phong Quoc Nguyen
7. Christos G Savva
8. Mark Hedglin
9. Samir M Hamdan
10. Alfredo De Biasio

• Curated by eLife

  eLife Assessment

  This paper reports new data on the structure of the human CTF18-RFC clamp loader complex bound to the PCNA clamp. The new and convincing data complement previous reports of CTF-RFC-PCNA structures and as such, represents an important contribution.

Reviewed by eLife

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. Amy M. Ehrlich
6. Charline Jomard
7. Jonas Brorson
8. Agnete N. Schou
9. Jean Farup
10. Julien Gondin
11. Jesper Just
12. Marc Foretz
13. Jonas T. Treebak
14. Marianne Agerholm
15. 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 toward a transcriptionally repressive state improves covalent inhibitor efficacy

1. Liudmyla Arifova
2. Brian S MacTavish
3. Zane Laughlin
4. Mithun Nag Karadi Girdhar
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