Biochemistry

The temperature dependence of binding entropy is a selective pressure in protein evolution

1. Rosemary Georgelin
2. Hannah Bott
3. Joe A. Kaczmarski
4. Rebecca Frkic
5. Li Lynn Tan
6. Nobuhiko Tokuriki
7. Matthew A. Spence
8. Colin J. Jackson

Reviewed by PREreview

Categorizing prediction modes within low-pLDDT regions of AlphaFold2 structures

1. Christopher J Williams
2. Vincent B Chen
3. David C Richardson
4. Jane S Richardson

Reviewed by Arcadia Science

Phage-displayed synthetic library and screening platform for nanobody discovery

1. Baolong Xia
2. Ah-Ram Kim
3. Feimei Liu
4. Myeonghoon Han
5. Emily Stoneburner
6. Stephanie Makdissi
7. Francesca Di Cara
8. Stephanie E Mohr
9. Aaron Ring
10. Norbert Perrimon

• Curated by eLife

  eLife Assessment

  This important study presents an alternative platform for nanobody discovery using phage-displayed synthetic libraries. The evidence supporting the platform, which is used to isolate and validate nanobodies targeting Drosophila secreted proteins, is compelling. By making the library openly accessible, this provides an excellent resource to the wider scientific community. The paper presents a detailed protocol for nanobody screening; as this protocol is refined and optimized over time, this will increase the success rate for discovering nanobodies with improved properties using this alternative platform.

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 identifies a novel Legionella effector, Lfat1, which binds F-actin via a coiled-coil domain and structurally resembles the RID toxin, with cryo-EM revealing key interactions mediated by a hydrophobic helical hairpin. While the study is mostly complete and has compelling data, a few minor changes are recommended.

Reviewed by eLife

Cardiolipin deficiency disrupts electron transport chain to drive steatohepatitis

1. Marisa J Brothwell
2. Guoshen Cao
3. J Alan Maschek
4. Annelise M Poss
5. Alek D Peterlin
6. Liping Wang
7. Talia B Baker
8. Justin L Shahtout
9. Piyarat Siripoksup
10. Quentinn J Pearce
11. Jordan M Johnson
12. Fabian M Finger
13. Alexandre Prola
14. Sarah A Pellizzari
15. Gillian L Hale
16. Allison M Manuel
17. Shinya Watanabe
18. Edwin R Miranda
19. Kajsa E Affolter
20. Trevor S Tippetts
21. Linda S Nikolova
22. Ran Hee Choi
23. Stephen T Decker
24. Mallikarjun Patil
25. J Leon Catrow
26. William L Holland
27. Sara M Nowinski
28. Daniel S Lark
29. Kelsey H Fisher-Wellman
30. Patrice N Mimche
31. Kimberley J Evason
32. James E Cox
33. Scott A Summers
34. Zach Gerhart-Hines
35. Katsuhiko Funai

• Curated by eLife

  eLife Assessment

  This paper reports on a correlation between diminished cardiolipin content and the severity of steatohepatitis in human subjects. This is supported further by experimental evidence from mice in which the gene encoding a key enzyme in cardiolipin synthesis has been compromised in the liver. The correlations established between lipidology, mitochondrial function, and the induction of respiration and oxidative stress are notable and will be useful to researchers in the field. However, given that the causal relationship between lipid perturbation and the progression of steatohepatitis implied in the title has not been tested experimentally, the evidence supporting the paper's key conclusion is incomplete.

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-Ling Lou
7. Tao-Feng Wei
8. Yun-Bi Lu
9. Tingting 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 results provide solid evidence to support the conclusions.

Reviewed by eLife

The Structural Dynamics of IRE1 and its Interaction with Unfolded Peptides

1. Elena Spinetti
2. G Elif Karagöz
3. Roberto Covino

• Curated by eLife

  eLife Assessment

  In this important study, the authors conducted atomistic molecular dynamics simulations to probe the interactions between IRE and unfolded peptides. The results help reconcile contradicting experimental findings in the literature and offer mechanistic insights into the activation of the unfolded protein response. The level of evidence is considered solid, although the use of enhanced sampling and more quantitative analysis would further strengthen the conclusions.

Reviewed by eLife

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

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