Biochemistry

NanoBlocks: creating fluorescent biosensors from affinity binders using competitive binding

1. Silke Denis
2. Vincent Van Deuren
3. Desiree I. Frecot
4. Ulrich Rothbauer
5. Shehab Ismail
6. Alison G. Tebo
7. Peter Dedecker

Reviewed by Arcadia Science

Intrinsic specificity of a 'core' Tip60 acetyltransferase complex in Drosophila

1. Silke Krause
2. Marco Borsò
3. Marisa Müller
4. Axel Imhof
5. Zivkos Apostolou
6. Peter B. Becker

Reviewed by Review Commons

Computational design of pH-sensitive binders

1. Green Ahn
2. Brian Coventry
3. Ella Haefner
4. Shayan Sadre
5. Jenny Hu
6. Mimosa Van
7. Buwei Huang
8. Isaac Sappington
9. Adam J. Broerman
10. Mauriz A. Lichtenstein
11. Matthias Glögl
12. Inna Goreshnik
13. Dionne Vafeados
14. David Baker

Reviewed by preLights

Integrated Respirometry and Metabolomics Unveil Circadian Metabolic Dynamics in Drosophila

1. Farheen Akhtar
2. Dania Malik
3. Arjun Sengupta
4. Paula Haynes
5. Jaco Klok
6. Amita Sehgal
7. Aalim M Weljie

• Curated by eLife

  eLife Assessment

  This study investigates how sleep loss and circadian disruption affect whole-organ metabolism in flies (Drosophila melanogaster) and reports that wild-type flies align metabolism in anticipation of diurnal rhythm, while mutant flies with impaired sleep or circadian function shift to reactive or misaligned metabolism. The integration of chamber-based flow-through respirometry with LC-MS metabolomics is innovative, and the significance of the findings is valuable. However, the strength of evidence needed to support the conclusions is incomplete based on concerns regarding the inappropriate use of constant darkness to disrupt circadian rhythms and the lack of details justifying the methods used to correlate respirometry data with whole-body metabolomics.

Reviewed by eLife

Structure-based Design of Chimeric Influenza Hemagglutinins to Elicit Cross-group Immunity

1. Karla M Castro
2. Reyhaneh Ayardulabi
3. Sarah Wehrle
4. Hongrui Cui
5. Sandrine Georgeon
6. Joseph Schmidt
7. Shuhao Xiao
8. Nishat Seraj
9. Wayne Harshbarger
10. Corey P Mallett
11. Ventzislav Vassilev
12. Xavier Saelens
13. Bruno E Correia

• Curated by eLife

  eLife Assessment

  This important study presents a thoughtful design and characterization of chimeric influenza hemagglutinin (HA) head domains combining elements of distinct receptor-binding sites. The results provide convincing evidence that polyclonal cross-group responses to influenza A virus can be elicited by a single immunization. While the mechanistic basis of heterotrimer formation and immunodominance differences remains unclear, the authors provide new insights for protein design, vaccinology, and computational vaccine design.

Reviewed by eLife

Structures of Multiple Peptide Resistance Factor from Pseudomonas aeruginosa

1. Shaileshanand Jha
2. Kutti R. Vinothkumar

Reviewed by Review Commons

Membrane-mimetic thermal proteome profiling (MM-TPP) toward mapping membrane protein–ligand dynamic interactions

1. Rupinder Singh Jandu
2. Ashim Bhattacharya
3. Frank Antony
4. Mohammed Al-Seragi
5. Hiroyuki Aoki
6. Mohan Babu
7. Franck Duong van Hoa

• Curated by eLife

  eLife Assessment

  This valuable study introduces the peptidisc-TPP approach as a promising solution to challenges in membrane proteomics, enabling thermal proteome profiling in a detergent-free system. The concept is innovative and holds significant potential, and the demonstration of its utility and validation is solid. The method presents a strong foundation for broader applications in identifying physiologically and pharmacologically relevant membrane protein-ligand interactions.

Reviewed by eLife

Cryo-EM structure revealed a novel F-actin binding motif in a Legionella pneumophila lysine fatty acyltransferase

1. Wenjie W Zeng
2. Garrison Komaniecki
3. Jiaze Liu
4. Hening Lin
5. Yuxin Mao

• Curated by eLife

  eLife Assessment

  This important study by Zeng et al characterizes a novel Legionella pneumophila effector, Llfat1 (Lpg1387), which binds actin through a newly identified actin-binding domain. Data is convincing; structural analysis of the Llfat1 ABD-F-actin complex enabled the development of this domain as a probe for F-actin. Additionally, the authors show that Llfat1 functions as a lysine fatty acyltransferase targeting small GTPases, highlighting its importance in both bacterial pathogenesis and cytoskeletal biology.

Reviewed by eLife

Mediator Subunit MED16 Collaborates with UBP1-TFCP2 to Control Transcriptional Activation or Repression via Promoter Positional Specificity

1. Yuanming Zheng
2. Xiaying Zhao
3. Ming Yang
4. Xinyi Yang
5. Huanzhang Zhu
6. Xiaofei Yu
7. Qiang Zhou
8. Gang Wang

• Curated by eLife

  eLife Assessment

  The characterization of a dissociable Mediator subunit implicated in cellular pathways, particularly lung alveolar function and HIV latency, would be conceptually interesting. The authors have preliminary evidence for a stable Med16 subcomplex that may regulate specific genes. This work is useful in that it points to interactions between Med16 and UBP1, but the evidence is preliminary and incomplete.

Reviewed by eLife

General trends in the calnexin-dependent expression and pharmacological rescue of clinical CFTR variants

1. Austin Tedman
2. John A Olson
3. Minsoo Kim
4. Catherine Foye
5. JaNise J Jackson
6. Eli F McDonald
7. Andrew G McKee
8. Karen Noguera
9. Charles P Kuntz
10. Jens Meiler
11. Kathryn E Oliver
12. Lars Plate
13. Jonathan P Schlebach

• Curated by eLife

  eLife Assessment

  This important study advances our understanding of how cellular quality control machinery influences cystic fibrosis (CF) drug responsiveness by systematically analyzing the effects of the chaperone calnexin on more than two hundreds of CFTR (cystic fibrosis transmembrane regulator) variants. The evidence supporting the conclusions is convincing, with a comprehensive deep mutational scanning methodology and rigorous quantitative analysis. The findings reveal that calnexin is critical for both CFTR protein expression and corrector drug efficacy in a variant-specific manner, providing invaluable insights that could guide the development of personalized CF therapies. This work will be of significant interest to researchers in protein folding, CF drug development, and genetic disease therapeutics.

Reviewed by eLife