Biophysics

Inorganic phosphate in Arp2/3 complex acts as a rapid switch for the stability of actin filament branches

1. Jiu Xiao
2. Rebecca Pagès
3. Guillaume Romet-Lemonne
4. Antoine Jégou

Reviewed by Review Commons

ADAPT-M: A workflow for rapid, quantitative in vitro measurements of enriched protein libraries

1. Carla P. Perez
2. Nicole V. DelRosso
3. Cameron L. Noland
4. Udit Parekh
5. Christian A. Choe
6. Raphael R. Eguchi
7. Qi Wen
8. Polly M. Fordyce
9. Po-Ssu Huang

Reviewed by Arcadia Science

Structural insights into the recruitment of viral Type 2 IRES to ribosomal preinitiation complex for protein synthesis

1. Deepakash Das
2. Tanweer Hussain

• Curated by eLife

  eLife Assessment

  This manuscript offers valuable structural and mechanistic insights into the assembly of the Type II internal ribosome entry site (IRES) from encephalomyocarditis virus (EMCV) and the translation initiation complex, revealing a direct interaction between the IRES and the 40S ribosomal subunit. A solid experimental strategy, combining cryo-EM analysis, complementary biochemistry, and detailed structural comparisons, provides mechanistic insights into IRES-based translation initiation systems. This paper will attract researchers in cap-independent translation, host-pathogen interactions, and virology.

Reviewed by eLife

Quantifying Intracellular Mechanosensitive Response upon Spatially Defined Mechano-Chemical Triggering

1. Elaheh Zare-Eelanjegh
2. Renard TM Lewis
3. Ines Lüchtefeld
4. Ulrike Kutay
5. Tomaso Zambelli

• Curated by eLife

  eLife Assessment

  This valuable study provides evidence that the integration of the nuclear envelope into the endoplasmic reticulum provides a mechanism for mechanical integration across this continuous membrane system. This work opens up new avenues for studying organelle membrane tension homeostasis. The evidence was found to be convincing and carefully quantified, with minor limitations that we expect to be further explored in future work.

Reviewed by eLife

Distinct energetic blueprints diversify function of conserved protein folds

1. Malcolm L. Wells
2. Chenlin Lu
3. Daniel Sultanov
4. Kyle C. Weber
5. Erin Ahern
6. Zhen Gong
7. Ethan Chen
8. Anum Glasgow

Reviewed by PREreview

Bifunctional Architecture Enables Substrate Catalysis and Channeling in Paracoccus TMAO Demethylase

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

• 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

Modulating inter-mitochondrial contacts to increase membrane potential for mitigating blue light damage

1. Yuxin Wang
2. Kangqiang Qiu
3. Weiwei Zou
4. Prativa Amom
5. Tushar H Ganjawala
6. Eugene Lee
7. Zhiqi Tian
8. Xiuqiong Xu
9. Taosheng Huang
10. Nien-Pei Tsai
11. Donglu Shi
12. Ping Kang
13. Hua Bai
14. Amanda L Zacharias
15. Kai Zhang
16. Jiajie Diao

• Curated by eLife

  eLife Assessment

  In this work, the authors demonstrated that blue light mediated mitochondrial contacts attenuated blue light induced mitochondrial dysfunction, and validated this in human cells and C. elegans. This valuable work has the potential to provide novel perspectives into the field of mitochondrial biology but the supporting data are incomplete.

Reviewed by eLife

DEER of Singly Labelled Proteins to Evaluate Supramolecular Packing of Amyloid Fibrils

1. Karen Tsay
2. Asif Equbal
3. Yuanxin Li
4. Tiffany Tsui
5. Songi Han
6. Yann Fichou

• Curated by eLife

  eLife Assessment

  This study presents a valuable methodological contribution exploiting the DEER background decay to quantify supramolecular packing in amyloid fibrils. The evidence is incomplete: the observation of D < 1 is inconsistent with the theoretical lower bound of the model, and it remains unclear whether this reflects a genuine systematic limitation or falls within experimental uncertainty.

Reviewed by eLife

Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity

1. Jordan M Mancl
2. Wenguang G Liang
3. Nicholas L Bayhi
4. Hui Wei
5. William C Budell
6. Joshua H Mendez
7. Tobin R Sosnick
8. Bridget Carragher
9. Clinton S Potter
10. Wei-Jen Tang

• Curated by eLife

  eLife Assessment

  The manuscript by Mancl et al. provides important mechanistic insights into the conformational dynamics of Insulin Degrading Enzyme (IDE), a zinc metalloprotease involved in the clearance of amyloid peptides. Supported by a compelling combination of time-resolved cryo-EM, SEC-SAXS, enzymatic assays, and both all-atom and coarse-grained simulations, the study reveals an insulin-induced allosteric transition and transient β-sheet interactions underlying IDE's unfoldase activity, thereby refining our understanding of IDE's functional cycle and offering a structural framework for developing substrate-selective modulators of M16 metalloproteases. The latest round of revisions further improves clarity and presentation by updating structural statistics, correcting minor textual inconsistencies, and refining supplemental materials, fully addressing the remaining reviewer comments.

Reviewed by eLife

Structural mechanisms of pump assembly and drug transport in the AcrAB–TolC efflux system

1. Xiaofei Ge
2. Zhiwei Gu
3. Jiawei Wang

• Curated by eLife

  eLife Assessment

  Ge et al here report a structural study of the native tripartite multidrug efflux pump complexes from Escherichia coli that identifies a novel accessory subunit, YbjP, the structure of the native TolC-YbjP-AcrABZ complex, as well as structures of the AcrB protein in L, T, and O conformations. The strength of the structural data is compelling, and the importance of the findings is potentially fundamental. In the revised manuscript, the authors have included additional analysis and made comparisons with pre-existing data which has helped place the data and its impact in the proper context.

Reviewed by eLife