Molecular Biology

A lipoprotein partner for the Escherichia coli outer membrane protein TolC

1. Jim Horne
2. Elise Kaplan
3. Ben Jin
4. Kieran Abbott
5. Victor Flores
6. Emmanouela Petsolari
7. Jan Gradon
8. Yvette Ntsogo
9. Andrzej Harris
10. Dingquan Yu
11. Ashraf Zarkan
12. Ben F Luisi

• Curated by eLife

  eLife Assessment

  In this fundamental work Horne et al present compelling evidence that YbjP is a novel binding partner of the TolC channel protein. The YbjP is characterized using cryo-EM, and its role probed using pull-down experiments, in vivo crosslinking, functional assays along with phylogenetic analysis which are all properly performed and presented and support the main conclusions. While the study does not identify a clear role for this protein, the revised manuscript offers improved clarity and contributes invaluable insight into membrane transport and antimicrobial resistance.

Reviewed by eLife

Interplay between cohesin and TORC1 links chromosome segregation and gene expression to environmental changes

1. Dorian Besson
2. Sabine Vaur
3. Stéphanie Vazquez
4. Sylvie Tournier
5. Yannick Gachet
6. Adrien Birot
7. Stéphane Claverol
8. Adèle L Marston
9. Anastasios Damdimopoulos
10. Karl Ekwall
11. Jean-Paul Javerzat

• Curated by eLife

  eLife Assessment

  This important study presents a compelling link between nutrient signaling and chromosome regulation, demonstrating that reduced activity in a central nutrient-sensing pathway improves chromosome stability and alters gene expression through effects on cohesin. The convincing evidence from a combination of genetic, biochemical and cell biological approaches supports a model in which TORC1-dependent phosphorylation of Mis4 and the cohesin subunit Psm1/Smc1 can modulate cohesin loading to enhance faithful chromosome transmission. While the underlying mechanisms and biological importance of this newly described circuit are not yet fully known, the overall body of evidence is strong and supports the main conclusions.

Reviewed by eLife

Herbivorous insects independently evolved salivary effectors to regulate plant immunity by destabilizing the malectin-LRR RLP NtRLP4

1. Xin Wang
2. Jia-Bao Lu
3. Yi-Zhe Wang
4. Xu-Hong Zhou
5. Jian-Ping Chen
6. Chuan-Xi Zhang
7. Jun-Min Li
8. Hai-Jian Huang

• Curated by eLife

  eLife Assessment

  This study provides an important contribution by showing that whiteflies and planthoppers use salivary effectors to suppress plant immunity through the receptor-like protein RLP4, suggesting convergent evolution in these insect lineages. The topic is of clear interest for understanding plant-insect interactions and offers ideas that could stimulate further research in the field. The authors provide convincing evidence for the functional roles of the salivary effectors.

Reviewed by eLife

Protein secretion routes in fungi are mostly determined by the length of the hydrophobic helix in the signal peptide

1. Tristan Sones-Dykes
2. Edward Wallace

Reviewed by Review Commons

The spike tip protein of bacteriophage T4

1. Yves Mattenberger
2. Ekaterina S Knyazhanskaya
3. Mikhail M Shneider
4. Sergey A Buth
5. Sergey Nazarov
6. William P Robins
7. Petr G Leiman
8. Dominique Belin

• Curated by eLife

  eLife Assessment

  This important study by Mattenburger et al. employs structural biology, biochemistry, and genetics to advance understanding of how bacteriophage contractile injection systems mediate host recognition and DNA delivery, yielding a remarkable 1.15 A crystal structure of the T4 spike tip complex (gp5-gp5.4). The compelling evidence presented demonstrates that the spike tip protein gp5.4 is essential for phage fitness and successful infection of Escherichia coli strains bearing truncated lipopolysaccharide; however, direct proof regarding interaction with the cell wall or its components is lacking. The study further provides biochemical evidence that the analogous spike tip protein from phage P2 (GpV) is translocated into the host periplasm during infection, together establishing the spike tip as a critical and active component of the phage infection machinery.

Reviewed by eLife

Systematic Analysis of Network-driven Adaptive Resistance to CDK4/6 and Estrogen Receptor Inhibition using Meta-Dynamic Network Modelling

1. Anthony Hart
2. Sung-Young Shin
3. Lan K Nguyen

• Curated by eLife

  eLife Assessment

  This manuscript presents a useful computational framework for systematically characterising how heterogeneity in initial conditions or biophysical parameters shapes the dynamic behaviour of protein signalling networks, with potential relevance to understanding adaptive drug resistance. While the approach represents a significant methodological contribution, the extent to which its conclusions are biologically informative remains debated, as the model is only qualitatively compared with experimental data and lacks quantitative validation. As a result, the strength of evidence supporting the mechanistic claims is viewed as incomplete.

Reviewed by eLife

Engineering ATP Import in Yeast Uncovers a Synthetic Route to Extend Cellular Lifespan

1. Naci Oz
2. Hetian Su
3. Vedat Sari
4. Praveen Patnaik
5. Rohil Hameed
6. Jong Hee Song
7. Derek C Prosser
8. Vyacheslav M Labunskyy
9. Vadim N Gladyshev
10. Nan Hao
11. Alaattin Kaya

• Curated by eLife

  eLife Assessment

  This manuscript addresses an important and conceptually ambitious question by using a synthetic biology strategy to perturb ATP homeostasis in yeast and examine its causal relationship with lifespan. While the experimental approach and lifespan data are intriguing, the current evidence is incomplete and internally inconsistent, particularly regarding intracellular ATP measurements, transporter directionality, mitochondrial dependence, and the proposed mechanistic model. Substantial clarification, additional controls, and further experimentation will be necessary before the main conclusions can be considered robust and the biological significance of the findings can be fully assessed.

Reviewed by eLife

Uncovering shared and tissue-specific molecular adaptations to intermittent fasting in liver, brain, and muscle

1. Yibo Fan
2. Senuri De Silva
3. Nishat I Tabassum
4. Xiangyuan Peng
5. Vernise JT Lim
6. Xiangru Cheng
7. Keshava K Datta
8. Rohan Lowe
9. Terrance G Johns
10. Mark P Mattson
11. Suresh Mathivanan
12. Christopher G Sobey
13. Eitan Okun
14. Yong U Liu
15. Guobing Chen
16. Mitchell Kim Peng Lai
17. Dong-Gyu Jo
18. Jayantha Gunaratne
19. Thiruma V Arumugam

• Curated by eLife

  eLife Assessment

  This is a solid paper on intermittent fasting that will be of interest to readers. The data presented are certainly valuable as a resource. The findings of both shared and tissue-specific signatures, both at the proteomic and transcriptomic levels, align well with what has been established and bring new insight into metabolic adaptation and its consequences in muscle, cortex, and liver. The organ specific changes unveiled by proteomics in response to IF reveal unique rewiring of metabolic, signaling and physiological function.

Reviewed by eLife

Structural basis for the folding of PINK1 by the HSP90–CDC37 chaperone complex

1. Kei Okatsu
2. Hayato Yamamoto
3. Akinori Okamoto
4. Shinya H Goto
5. Yumiko Nishimoto
6. Yukihiko Sugita
7. Takeshi Noda
8. Shuya Fukai

• Curated by eLife

  eLife Assessment

  This study presents a high-quality cryo-EM structure of the human kinase PINK1 in complex with the HSP90-CDC37 chaperone complex, capturing a partially folded intermediate in which the C-lobe and C-terminal extension are structured while the N-lobe remains unfolded and engaged by the HSP90 clamp. The structural data are broadly consistent with a recently published structure of the same complex, providing useful insight into early steps of PINK1 maturation and highlighting residues linked to familial Parkinson's disease. However, the mechanistic conclusions remain incomplete because the manuscript does not experimentally validate key hypotheses raised by the structure, including the functional roles of the C-lobe interface, the HPNI motif, the C-terminal extension, or the proposed competition between HSP90 and TOM20.

Reviewed by eLife

Global molecular landscape of early MASLD progression in human obesity

1. Qing Zhao
2. William De Nardo
3. Ruoyu Wang
4. Yi Zhong
5. Umur Keles
6. Gabriele Sakalauskaite
7. Li Na Zhao
8. Huiyi Tay
9. Sonia Youhanna
10. Mengchao Yan
11. Ye Xie
12. Youngrae Kim
13. Sungdong Lee
14. Rachel Liyu Lim
15. Guoshou Teo
16. Pradeep Narayanaswamy
17. Paul R Burton
18. Volker M Lauschke
19. Hyungwon Choi
20. Matthew J Watt
21. Philipp Kaldis

• Curated by eLife

  eLife Assessment

  The authors provide a useful resource and approach to identify early-stage biomarkers of MASLD progression, notably when no other apparent symptoms have arisen. The strength of evidence to support new MASLD signatures is solid as the work combines metabolomic and transcriptomic measures in blood and liver biopsies.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons