Biochemistry

Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays

1. Jonathan G Van Vranken
2. Jiaming Li
3. Julian Mintseris
4. Ting-Yu Wei
5. Catherine M Sniezek
6. Meagan Gadzuk-Shea
7. Steven P Gygi
8. Devin K Schweppe

• Curated by eLife

  eLife Assessment

  The study provides a valuable showcase of a workflow to perform large-scale characterization of drug mechanisms of action using proteomics in which on-target and off-targets of 166 compounds using proteome solubility analysis in living cells and cell lysates were determined. The evidence supporting the claims of the authors is solid, however, the inclusion of more replicate experiments and more statistical rigor would have strengthened the study. This will be of broad interest to medicinal chemists, toxicologists, computational biologists and biochemists

Reviewed by eLife

A new class of receptors: Lipids regulate mammalian Gsα-stimulated adenylyl cyclase activities via their membrane anchors

1. Marius Landau
2. Sherif Elsabbagh
3. Harald Gross
4. Adrian Fuchs
5. Anita CF Schultz
6. Joachim E Schultz

• Curated by eLife

  eLife Assessment

  This manuscript describes a valuable study of a new lipid-mediated regulation mechanism of adenylyl cyclases. The biochemical evidence provided is convincing, but more evidence for regulation by lipids under natural cellular processes would be interesting. This manuscript will be of interest to all scientists working on lipid regulation and adenylyl cyclases.

Reviewed by eLife, Arcadia Science

The intrinsically disordered N-terminus of SUMO1 is an intramolecular inhibitor of SUMO1 interactions

1. Sebastian M Richter
2. Fan Jin
3. Tobias Ritterhoff
4. Aleksandra Fergin
5. Eric Maurer
6. Andrea Frank
7. Michael Daube
8. Alex Hajnal
9. Rachel Klevit
10. Frauke Gräter
11. Annette Flotho
12. Frauke Melchior

• Curated by eLife

  eLife assessment

  This work demonstrates an important regulatory role of the N-terminal disordered tail of small ubiquitin-like modifier (SUMO) proteins, which modulate the function of various proteins in eukaryotic cells. The authors present convincing evidence that the N-terminal tail of SUMO inhibits SUMO's interaction with downstream effector proteins and SUMOylation targets, and that this regulatory mechanism depends on the SUMO paralogue or the phosphorylation of the N-terminal tail. This discovery significantly advances the field by providing a possible explanation of how SUMO paralogues select their effectors and SUMOylation targets.

Reviewed by eLife

Elucidating the kinetic and thermodynamic insight into regulation of glycolysis by lactate dehydrogenase and its impact on tricarboxylic acid cycle and oxidative phosphorylation in cancer cells

1. Siying Zeng
2. Yuqi Wang
3. Minfeng Ying
4. Chengmeng Jin
5. Chang Ying
6. Di Wang
7. Hao Wu
8. Xun Hu

• Curated by eLife

  eLife assessment

  This study presents an assessment of the effect of lactate dehydrogenase (LDH) inhibition on the activity of glycolysis and tricarboxylic acid cycle. The data were collected and analyzed using solid and validated methodology. This paper makes a useful contribution to the field as it considers a control analysis of LDH flux.

Reviewed by eLife

Bioorthogonal labeling of chitin in pathogenic Candida species reveals biochemical mechanisms of hyphal growth and homeostasis

1. Caroline Williams
2. Bella R. Carnahan
3. Stephen N. Hyland
4. Catherine L. Grimes

Reviewed by PREreview

Elucidating ATP’s Role as Solubilizer of Biomolecular Aggregate

1. Susmita Sarkar
2. Saurabh Gupta
3. Chiranjit Mahato
4. Dibyendu Das
5. Jagannath Mondal

• Curated by eLife

  eLife assessment

  The authors combined molecular dynamics simulations and experiments to study the role of ATP as a hydrotrope of protein aggregates. The topic is of major current interest and thus the study potentially makes an important contribution to the community. With the revised version, the level of evidence is considered generally solid, although there remains concern regarding the unusually high ATP concentration used in the simulation.

Reviewed by eLife

Stabilization of GTSE1 by cyclin D1-CDK4/6 promotes cell proliferation: relevance in cancer prognosis

1. Nelson García-Vázquez
2. Tania J González-Robles
3. Ethan Lane
4. Daria Spasskaya
5. Qingyue Zhang
6. Marc Kerzhnerman
7. YeonTae Jeong
8. Marta Collu
9. Daniele Simoneschi
10. Kelly V Ruggles
11. Gergely Rona
12. Michele Pagano
13. Sharon Kaisari

• Curated by eLife

  eLife assessment

  In this valuable study, García-Vázquez et al. provide solid evidence suggesting that G2 and S phases expressed protein 1 (GTSE1), is a previously unappreciated non-pocket substrate of cyclin D1-CDK4/6 kinases. To this end, this study holds a promise to significantly contribute to an improved understanding of the mechanisms underpinning cell cycle progression. Notwithstanding these clear strengths of the article, it was thought that the study may benefit from establishing the precise role of cyclin D1-CDK4/6 kinase-dependent GTSE1 phosphorylation in the context of cell cycle progression, obtaining more direct evidence that cyclin D1-CDK4/6 kinase phosphorylate indicated sites on GTSE1 (e.g., S454) and mapping a degron in GTSE1 whose function may be blocked by cyclin D1-CDK4/6 kinase-dependent phosphorylation.

Reviewed by eLife

Dimer-monomer transition defines a hyper-thermostable peptidoglycan hydrolase mined from bacterial proteome by lysin-derived antimicrobial peptide-primed screening

1. Li Zhang
2. Fen Hu
3. Zirong Zhao
4. Xinfeng Li
5. Mingyue Zhong
6. Jiajun He
7. Fangfang Yao
8. Xiaomei Zhang
9. Yuxuan Mao
10. Hongping Wei
11. Jin He
12. Hang Yang

• Curated by eLife

  eLife assessment

  This valuable study explores a new strategy of lysin-derived antimicrobial peptide-primed screening to find peptidoglycan hydrolases from bacterial proteomes. Using this strategy, the authors identified five peptidoglycan hydrolases from Acinetobacter baumannii, which they tested on various Gram-positive and Gram-negative pathogens for antimicrobial activity. The revised manuscript addressed most of the prior concerns, and the data presented are solid and will be of interest to microbiologists.

Reviewed by eLife

Disordered proteins interact with the chemical environment to tune their protective function during drying

1. Shraddha KC
2. Kenny Nguyen
3. Vincent Nicholson
4. Annie Walgren
5. Tony Trent
6. Edith Gollub
7. Sofia Romero
8. Alex S Holehouse
9. Shahar Sukenik
10. Thomas C Boothby

• Curated by eLife

  eLife assessment

  This important study investigates the sensitivity to endogenous cosolvents of three families of intrinsically disordered proteins involved with desiccation. The findings, drawn from well-designed experiments and calculations, suggest a functional synergy between sensitivity to small molecule solutes and convergent desiccation protection strategy. The evidence is found to be convincing, and the authors provide appropriate caveats since the study's conclusions are based on a small number of proteins. This work will be of interest to biochemists and biophysicists interested in the conformation-function relationship of intrinsically disordered proteins.

Reviewed by eLife

Early Steps of Protein Disaggregation by Hsp70 Chaperone and Class B J-Domain Proteins are Shaped by Hsp110

1. Wiktoria Sztangierska
2. Hubert Wyszkowski
3. Maria Pokornowska
4. Klaudia Kochanowicz
5. Michał Rychłowski
6. Krzysztof Liberek
7. Agnieszka Kłosowska

• Curated by eLife

  eLife assessment

  This study provides an important insight into the mechanisms of cooperation between Hsp70 and its cochaperones during reactivation of aggregated proteins. Based on convincing evidence, the authors demonstrate that the co-chaperone Hsp110 boosts disaggregation activity by enhancing Hsp70 recruitment to protein aggregates. This work is of broad interest to biochemists and cell biologists working in the protein homeostasis field.

Reviewed by eLife