eLife

Latest preprint reviews

1. Cul5Wsb2 uses BCL2 proteins as co-receptors to target Bim for degradation

   This article has 4 authors:

   1. Wilhelm Vaysse-Zinkhöfer
   2. Enya Marie Catherine Alcindor
   3. Nicholas Garaffo
   4. David Paul Toczyski

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     The study presents a valuable finding on the ubiquitin-dependent regulatory loop in which proapoptotic Bim is targeted to the E3 ubiquitin ligase Cul5-Wsb2-mediated degradation through its sequestration by BCL2 proteins. The conclusions are supported by incomplete evidence and would benefit from additional experiments addressing both the mechanistic understanding and the physiological/cancer-related significance of the study.

   Reviewed by eLife

2. Adaptation of an herbivorous arthropod to green tea plants by overcoming catechin defenses

   This article has 10 authors:

   1. Naoki Takeda
   2. Brendan Abiskaroon
   3. Ricardo Hernandez Arriaza
   4. Ryutaro Murakami
   5. Shogo Sasaki
   6. Masanobu Yamamoto
   7. Vladimir Zhurov
   8. Vojislava Grbić
   9. Maksymilian Chruszcz
   10. Takeshi Suzuki

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study provides mechanistic evidence that tea-adapted two-spotted spider mite overcomes green tea catechin defenses via the horizontally transferred dioxygenase TkDOG15, supporting a two-step adaptation model, combining enzyme refinement and inducible upregulation. The evidence is convincing because multi-omics signals converge with functional validation (RNAi knockdown and recombinant enzyme assays) and well-controlled behavioral/toxicity assays to link TkDOG15 activity and expression to survival and feeding on tea.

   Reviewed by eLife

3. A structural code for assembly specificity in GID/CTLH-type E3 ligases

   This article has 2 authors:

   1. Pia Maria van gen Hassend
   2. Hermann Schindelin

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This structural biology study provides insights into the assembly of the GID/CTLH E3 ligase complex. The multi-subunit complex forms unique, ring-shaped assemblies and the findings presented here describe a "specificity code" that regulates formation of subunit interfaces. The data supporting the conclusions are convincing, both in thoroughness and rigor. This study will be valuable to biochemists, structural biologists, and could lay foundation for novel designed protein assemblies.

   Reviewed by eLife

4. A novel RAB5 binding site in human VPS34-CII that is likely the primordial site in eukaryotic evolution

   This article has 5 authors:

   1. Saule Spokaite
   2. Yohei Ohashi
   3. Maxime Bourguet
   4. Antoine Nicolas Dessus
   5. Roger L Williams

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This convincing study examines a novel interaction of RAB5 with VPS34 complex II. Structural data are combined with site-directed mutagenesis, sequence analysis, biochemistry, yeast mutant analysis, and prior data on RAB1-VPS34 and RAB5-VPS34 interactions to provide a new perspective on how RAB GTPases recruit related but distinct VPS34 complexes to different organelles. The judgment is that this work represents a fundamental advance in our understanding of VPS34 localization and regulation.

   Reviewed by eLife

5. Interrogating the structure and function of the human voltage-gated proton channel (hHv1) with a fluorescent noncanonical amino acid

   This article has 3 authors:

   1. Emerson M Carmona
   2. William N Zagotta
   3. Sharona E Gordon

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This important study presents a convincing methodological approach to probe the structural features of the full-length human Hv1 channel as a purified protein. The method is supported by rigorous biochemical assays and spectral FRET analysis, which will interest biophysicists and physiologists studying Hv1 and other ion channels and membrane proteins. Overall, the work introduces an interesting labeling strategy and provides a methodology that is of value in investigating hHV1 in particular and can be extended to other ion channels. The authors also provide preliminary observations regarding conformational changes induced by zinc.

   Reviewed by eLife

6. Developmental sleep reallocation enables metabolic adaptation in desert flies

   This article has 6 authors:

   1. Shuhao Li
   2. Milan Szuperak
   3. Ceazar Nave
   4. Si Hao Tang
   5. Jeffrey M Donlea
   6. Matthew S Kayser

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     Li et al. present an important and innovative study linking developmental changes in sleep to ecological context in Drosophila mojavensis, and propose that sleep at one stage of an animal's life might anticipate needs at a future stage. The results fit well with this model, but are correlative in nature. The work is convincing, scientifically rigorous, and effectively bridges sleep biology and evolutionary ecology, opening promising new directions for the field.

   Reviewed by eLife

7. Long Wake/Short Sleep Bouts and Hyperactivity with Advanced Age in a Mouse Model of Early Onset Alzheimer’s Disease

   This article has 9 authors:

   1. Ryan K Tisdale
   2. Yu Sun
   3. Stephanie R Miller
   4. Stephanie M Lee
   5. Sunmee Park
   6. Jia Shin
   7. Giancarlo Allocca
   8. Jorge J Palop
   9. Thomas S Kilduff

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This study provides useful insights regarding the alterations of sleep architecture in a knock-in mouse model of Alzheimer's Disease (AD). These include age-related hyperactivity that is typically associated with increased arousal, a normal homeostatic response to sleep loss, and a stronger AD-like phenotype in females. Although the analyses are robust, evidence for the proposed mechanisms underlying abnormal sleep architecture is incomplete. Overall, the study may have a focused impact for the sleep and AD fields.

   Reviewed by eLife

8. Drosophila melanogaster model of RVCL-S demonstrates age dependent disease progression

   This article has 9 authors:

   1. Elena Gracheva
   2. Abigail Matt
   3. Fei Wang
   4. Raymond Hsin
   5. Hongwu Liang
   6. Xiangping Ouyang
   7. Jimin Ding
   8. Jonathan J Miner
   9. Chao Zhou

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript describing the phenotypes associated with loss and gain of RVCL-S documents important findings that have practical implications. Although the data and methods are solid and support many claims, there remain some concerns about mechanisms.

   Reviewed by eLife

9. Bifunctional Architecture Enables Substrate Catalysis and Channeling in Paracoccus TMAO Demethylase

   This article has 8 authors:

   1. Trung Thach
   2. KanagaVijayan Dhanabalan
   3. Shiwangi Maurya
   4. Yu Han-Hallet
   5. Senwei Quan
   6. Jane Allison
   7. Gurunath Ramanathan
   8. Ramaswamy Subramanian

   This article has been curated by 1 group:

   • Curated by eLife

     eLife Assessment

     This manuscript reports high-resolution cryo-EM structures of a trimethylamine N-oxide demethylase and advances the hypothesis that the enzyme is bifunctional, coupling TMAO demethylation to formaldehyde capture via an enclosed intramolecular tunnel. The structural findings remain valuable, particularly the unusual oligomeric architecture and proposed conduit for a reactive intermediate. While the revision improves clarity and addresses several technical concerns, the central mechanistic framework remains incomplete, with persistent concerns regarding the proposed catalytic mechanism and metal dependence.

   Reviewed by eLife

10. Distinct Mechanisms for Inhibition of SARS-CoV-2 Main Protease: Dimerization Promoted by Peptidomimetic Inhibitors and Disrupted by Ebselen

    This article has 4 authors:

    1. Chengxi Liu
    2. Qinyu Jia
    3. Chang Zhao
    4. Zhong-Ping Yao

    This article has been curated by 1 group:

    • Curated by eLife

      eLife Assessment

      This important study provides a comprehensive comparison of the mechanisms through which different inhibitors affect the SARS-CoV-2 main protease, a pivotal antiviral drug target, and suggests a potentially broad-spectrum strategy to inhibit this critical viral enzyme by disrupting its dimerization states. However, whereas the biophysical analyses of the dimer stability are convincing, evidence supporting this new mode of mechanism to inhibit the main protease is incomplete and would benefit from a correlation of the biophysical observations with functional activity. With the functional validation part strengthened, this work would be of interest to biochemists and virologists working on anti-coronavirus drug discovery.

    Reviewed by eLife