Biochemistry

One-carbon metabolism enzyme Ahcy is a redox sensor that modulates gene expression to protect against light stress-induced retinal degeneration

1. Sarah C. Stanhope
2. Kratika Singhal
3. Nicolás M. Morato
4. Yunfei Feng
5. Gaoya Meng
6. Makayla N. Marlin
7. Claudia C. Kotanko
8. Madolyn M. Jarrett
9. Andrew D. Mesecar
10. Graham R. Cooks
11. Vikki M. Weake

Reviewed by PREreview

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, structural, and cellular approaches, the authors show that covalent inhibitors with inverse agonist activities modulate receptor conformation to permit co-binding with additional ligands, leading to a finely tuned transcriptional response. The data support a model of proximal, bi-directional allostery that challenges traditional views of nuclear receptor regulation. These findings will be of broad interest to researchers in structural biology, transcriptional control, and drug discovery.

Reviewed by eLife

In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer

1. Edward P. Harvey
2. Jeffrey S. Smith
3. Joseph D. Hurley
4. Alyana Granados
5. Ernst W. Schmid
6. Jason G. Liang-Lin
7. Steffanie Paul
8. Emily M. Meara
9. Matthew P. Ferguson
10. Victor G. Calvillo-Miranda
11. Debora S. Marks
12. Johannes C. Walter
13. Andrew C. Kruse
14. Katherine J. Susa

Reviewed by Arcadia Science

Fibroblast growth factor 21 regulates neuromuscular junction innervation through HDAC4 in denervation-induced skeletal muscle atrophy

1. Lirong Zheng
2. Takashi Sasaki
3. Liyang Ni
4. Yu Takahashi
5. Yoshio Yamauchi
6. Makoto Shimizu
7. Sato Ryuichiro

Reviewed by preLights

Development of D-box peptides to inhibit the anaphase-promoting complex/cyclosome

1. Rohan Eapen
2. Cynthia Okoye
3. Christopher Stubbs
4. Marianne Schimpl
5. Thomas Tischer
6. Eileen J Fisher
7. Maria Zacharopoulou
8. Fernando Ferrer
9. David Barford
10. David R Spring
11. Catherine Lindon
12. Christopher Phillips
13. Laura S Itzhaki

• Curated by eLife

  eLife Assessment

  The manuscript represents a fundamental advance in designing peptide inhibitors targeting Cdc20, a key activator and substrate-recognition subunit of the APC/C ubiquitin ligase. Supported by compelling biophysical and cellular evidence, the study lays a strong foundation for future developments in degron-based therapeutics. The revised manuscript has been strengthened by additional clarifications and data that address prior reviewer concerns. The work provides a robust framework for developing tools to manipulate protein degradation and will be of broad interest to researchers in protein engineering, cell cycle regulation, and targeted protein degradation.

Reviewed by eLife

Solubilization of Membrane Proteins using designed protein WRAPS

1. Ljubica Mihaljević
2. David E. Kim
3. Helen E. Eisenach
4. Pooja D. Bandawane
5. Andrew J. Borst
6. Alexis Courbet
7. Everton Bettin
8. Qiushi Liu
9. Connor Weidle
10. Sagardip Majumder
11. Xinting Li
12. Mila Lamb
13. Analisa Nicole Azcárraga Murray
14. Rashmi Ravichandran
15. Elizabeth C. Williams
16. Shuyuan Hu
17. Lynda Stuart
18. Linda Grillová
19. Nicholas R. Thomson
20. Pengxiang Chang
21. Melissa J. Caimano
22. Kelly L. Hawley
23. Neil P. King
24. David Baker

Reviewed by Rapid Reviews Infectious Diseases

Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences

1. Elise Miedlar
2. Grace E Hamilton
3. Samuel R Witus
4. Sara J Gonske
5. Michael Riffle
6. Alex Zelter
7. Rachel E Klevit
8. Charles L Asbury
9. Yoana N Dimitrova
10. Trisha N Davis

• Curated by eLife

  eLife Assessment

  Centromeres are specific sites on chromosomes that are essential for mitosis and genome fidelity. This valuable research advance builds upon previous studies to convincingly show that the centromere-histone core contributes to force transduction through the kinetochore. The centromere mainly strengthens one of the two paths of force transduction, influenced by the centromeric DNA sequence. The mechanism underlying this phenomenon will be an exciting future avenue of research, given that centromeric DNAs are not conserved. This work will be of interest to those studying cell division and chromosome segregation.

Reviewed by eLife

Trifluoroacetate reduces plasma lipid levels and the development of atherosclerosis in mice

1. Wei Tang
2. Audrey S. Black
3. Romana Moench
4. Katayoon Marzban
5. Juan Antonio Raygoza Garay
6. James J. Zheng
7. Louis Conway
8. Antonio F. M. Pinto
9. Christopher G. Parker
10. Alan Saghatelian
11. Luke J. Leman
12. M. Reza Ghadiri

Reviewed by PREreview

Heterooligomerization drives structural plasticity of eukaryotic peroxiredoxins

1. Jannik Zimmermann
2. Lukas Lang
3. Julia Malo Pueyo
4. Mareike Riedel
5. Khadija Wahni
6. Dylan Stobbe
7. Christopher Lux
8. Steven Janvier
9. Didier Vertommen
10. Svenja Lenhard
11. Frank Hannemann
12. Helena Castro
13. Ana Maria Tomas
14. Johannes M. Herrmann
15. Armindo Salvador
16. Timo Mühlhaus
17. Jan Riemer
18. Joris Messens
19. Marcel Deponte
20. Bruce Morgan

Reviewed by PREreview

Mycobacterial EsxG·EsxH (TB9.8·TB10.4) peptides as a subunit vaccine to booster BCG vaccination in an experimental model of pulmonary Tuberculosis

1. Constanza Estefania Martínez-Olivares
2. Vasti Lozano-Ordaz
3. Dulce Mata-Espinosa
4. Jorge Alberto Barrios-Payán
5. Ángel Elías Ortiz-Cabrera
6. Yadira Rocio Rodríguez-Miguez
7. Rogelio Hernández-Pando

Reviewed by PREreview