Biochemistry

Conformational dynamics and asymmetry in multimodal inhibition of membrane-bound pyrophosphatases

1. Jianing Liu
2. Anokhi Shah
3. Xinyu Liu
4. Joshua L Wort
5. Yue Ma
6. Katie Hardman
7. Niklas G Johansson
8. Orquidea Ribeiro
9. Adam Brookfield
10. Alice Bowen
11. Jari Yli-Kauhaluoma
12. Henri Xhaard
13. Lars JC Jeuken
14. Adrian Goldman
15. Christos Pliotas
16. Keni Vidilaseris

• Curated by eLife

  eLife Assessment

  This important study uncovers the mechanism of inhibition of a membrane pyrophosphatase by non-hydrolyzable phosphonate substrate analogs. Convincing crystallography, EPR spectroscopy, and functional measurements support the presence of a distinct conformational equilibrium of TmPPase in solution, and further supports the notion of asymmetric inhibitor binding at the active site, while maintaining a symmetric conformation at the periplasmic interface.

Reviewed by eLife

Mapping Cryptic Phosphorylation Sites in the Human Proteome

1. Dino Gasparotto
2. Annarita Zanon
3. Valerio Bonaldo
4. Elisa Marchiori
5. Massimo Casagranda
6. Erika Di Domenico
7. Laura Copat
8. Tommaso Fortunato Asquini
9. Marta Rigoli
10. Sirio Vittorio Feltrin
11. Nuria Lopez Lorenzo
12. Graziano Lolli
13. Maria Pennuto
14. Jesùs R. Requena
15. Omar Rota Stabelli
16. Giovanni Minervini
17. Cristian Micheletti
18. Giovanni Spagnolli
19. Pietro Faccioli
20. Emiliano Biasini

Reviewed by Review Commons

Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes

1. Janelle JY Chuah
2. Madalena R Daugherty
3. David M Smith

• Curated by eLife

  eLife Assessment

  This useful manuscript describes cryo-EM structures of archaeal proteasomes that reveal insights into how occupancy of binding pockets on the 20S protease regulates proteasome gating. The evidence supporting these claims is convincing, although inclusion of more quantitative comparisons would help strengthen the conclusions. This work will be of special interest to researchers interested in proteasome structure and regulation.

Reviewed by eLife

Structural insights into heterohexameric assembly of epilepsy-related ligand–receptor complex LGI1–ADAM22

1. Takayuki Yamaguchi
2. Kei Okatsu
3. Masato Kubota
4. Ayuka Mitsumori
5. Atsushi Yamagata
6. Yuko Fukata
7. Masaki Fukata
8. Mikihiro Shibata
9. Shuya Fukai

• Curated by eLife

  eLife Assessment

  In this convincing work by Yamaguchi et al. the cryo-EM structure of the heterohexameric 3:3 LGI1-ADAM22 complex is presented. The findings suggest that LGI1 can cluster ADAM22 in a trimeric fashion. The clustering of cell surface proteins is important in controlling signaling in the nervous system. This new version of the manuscript has been improved substantially and the figures have been enhanced and clarified.

Reviewed by eLife

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

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 T Rao
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