Biochemistry

A novel broad-spectrum antibiotic targets multiple-drug-resistant bacteria with dual binding targets and no detectable resistance

1. Wenyan He
2. Xueting Huan
3. Yinchuan Li
4. Qisen Deng
5. Tao Chen
6. Wen Xiao
7. Yijun Chen
8. Lingman Ma
9. Nan Liu
10. Zhuo Shang
11. Zongqiang Wang

Reviewed by Rapid Reviews Infectious Diseases

Gut Microbe-Derived Trimethylamine Shapes Circadian Rhythms Through the Host Receptor TAAR5

1. Kala K Mahen
2. William J Massey
3. Danny Orabi
4. Amanda L Brown
5. Thomas C Jaramillo
6. Amy C Burrows
7. Anthony J Horak
8. Sumita Dutta
9. Marko Mrdjen
10. Nour Mouannes
11. Venkateshwari Varadharajan
12. Lucas J Osborn
13. Xiayan Ye
14. Dante M Yarbrough
15. Treg Grubb
16. Natalie Zajczenko
17. Rachel Hohe
18. Rakhee Banerjee
19. Pranavi Linga
20. Dev Laungani
21. Adeline M Hajjar
22. Naseer Sangwan
23. Mohammed Dwidar
24. Jennifer A Buffa
25. Garth R Swanson
26. Zeneng Wang
27. J Mark Brown

• Curated by eLife

  eLife Assessment

  This study presents an important finding linking the bacterial metabolite trimethylamine and its receptor to circadian rhythms and olfaction. The current evidence supporting the claims of the authors is convincing, although further data and improvements to the presentation would further increase the impact of these results. This work will be of broad interest to researchers interested in nutrition, microbial metabolism, circadian rhythms, and host-microbiome interactions.

Reviewed by eLife

RamanMAE: Masked Autoencoders Enable Efficient Molecular Imaging by Learning Biologically Meaningful Spectral Representations

1. Santosh Kumar Paidi
2. Parul Maheshwari

Reviewed by Arcadia Science

Membrane curvature regulates Ups1 dependent phosphatidic acid transfer across lipid bilayers

1. Fereshteh Sadeqi
2. Dexin Dong
3. Kai Stroh
4. Marian Vache
5. Jutta Metz
6. Dietmar Riedel
7. Andreas Janshoff
8. Herre Jelger Risselada
9. Caroline Kolenda
10. Michael Meinecke

• Curated by eLife

  eLife Assessment

  This fundamental study combines in vitro reconstitution experiments and molecular dynamics simulations to elucidate how membrane lipids are transported from the outer to the inner membrane of mitochondria. The authors provide convincing evidence that a positive membrane curvature is critical for membrane lipid extraction. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife

Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers

1. Xiaoyu Yu
2. Yuanjun He
3. Theodore M Kamenecka
4. Douglas J Kojetin

• Curated by eLife

  eLife Assessment

  This important study investigated whether the nuclear receptor Nur77 is regulated by a non-canonical mechanism of ligand-induced disruption of its interaction with RXRg, similar to the family member Nurr1. The overall evidence is solid, but additional mechanisms that have not been fully explored in this study might contribute as well. This manuscript will be of interest to scientists focusing on mechanisms of transcriptional regulation.

Reviewed by eLife

Elevated Ubiquitin Phosphorylation by PINK1 Contributes to Proteasomal Impairment and Promotes Neurodegeneration

1. Cong Chen
2. Tong-Yao Gao
3. Hua-Wei Yi
4. Yi Zhang
5. Tong Wang
6. Zhi-Lin Lou
7. Tao-Feng Wei
8. Yun-Bi Lu
9. Ting-Ting Li
10. Chun Tang
11. Wei-Ping Zhang

• Curated by eLife

  eLife Assessment

  This study provides important insights into the role of polyUbiquitination in neurodegenerative diseases, elucidating how pUb promotes neurodegeneration by affecting proteasomal function. The findings not only offer a new perspective on the pathophysiology of neurodegenerative diseases but also provide potential targets for developing new therapeutic strategies. The experiments in the revised submission provide solid evidence to support the conclusions.

Reviewed by eLife

Dual-specific autophosphorylation of kinase IKK2 enables phosphorylation of substrate IκBα through a phosphoenzyme intermediate

1. Prateeka Borar
2. Tapan Biswas
3. Ankur Chaudhuri
4. Pallavi Rao T
5. Swasti Raychaudhuri
6. Tom Huxford
7. Saikat Chakrabarti
8. Gourisankar Ghosh
9. Smarajit Polley

• Curated by eLife

  eLife Assessment

  This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. The findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.

Reviewed by eLife

Energetic and structural control of polyspecificity in a multidrug transporter

1. Silas T. Miller
2. Katherine A. Henzler-Wildman
3. Srivatsan Raman

Reviewed by PREreview

Growth inhibitory factor/metallothionein-3 is a sulfane sulfur-binding protein

1. Yasuhiro Shinkai
2. Yunjie Ding
3. Toru Matsui
4. George Devitt
5. Masahiro Akiyama
6. Tang-Long Shen
7. Motohiro Nishida
8. Tomoaki Ida
9. Takaaki Akaike
10. Sumeet Mahajan
11. Jon M Fukuto
12. Yasuteru Shigeta
13. Yoshito Kumagai

• Curated by eLife

  eLife Assessment

  This valuable work provides solid evidence that a neuronal metallothionein, GIF/MT-3, incorporates metal-persulfide clusters. A variety of well-designed assays support the authors' hypothesis, revealing that sulfane sulfur is released from MT-3. However, the sufane sulfur content in the canonical induced MT-1 and MT-2 has not been demonstrated. Thus, the biological role of the persulfidated form is not yet clearly defined. There are caveats to the findings that limit the study, but the work will nevertheless prompt major follow-up work.

Reviewed by eLife

The alternative oxidase reconfigures the larval mitochondrial electron transport system to accelerate growth and development in Drosophila melanogaster

1. Geovana S Garcia
2. Murilo F Othonicar
3. Antonio Thiago P Campos
4. Eric A Kilbourn
5. Kênia C Bícego
6. Johannes Lerchner
7. Jason M Tennessen
8. Marcos T Oliveira

• Curated by eLife

  eLife Assessment

  The findings in this manuscript are important because they demonstrate the key role of metabolism in insect development. The data were collected and analyzed using solid and validated methodologies, but the evidence is incomplete, as the extent of the involvement of AOX activity in vivo and in physiological conditions is not addressed. This manuscript will be of interest for the fields of mitochondrial bioenergetics, metabolism and development.

Reviewed by eLife