Biophysics

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

Differential interfacial tension between oncogenic and wild-type populations forms the mechanical basis of tissue-specific oncogenesis in epithelia

1. Amrapali Datta
2. Phanindra Dewan
3. Aswin Anto
4. Tanya Chhabra
5. Tanishq Tejaswi
6. Sindhu Muthukrishnan
7. Akshar Rao
8. Sumantra Sarkar
9. Medhavi Vishwakarma

• Curated by eLife

  eLife Assessment

  This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This is explained by hypothesising the existence of a heterotypic tension at the boundary between different cell types, and supported by pharmacological perturbations and numerical simulations using the vertex model. The solid study conveys a key message, although some uncertainty remains regarding the origin of the heterotypic tension in relation to acto-myosin organisation in the boundary cells.

Reviewed by eLife

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 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

Seeing in the Dark: Intelligent Fourier Light Field Imaging for Bioluminescence Microscopy

1. Luis Felipe Morales Curiel
2. Michael Krieg

Reviewed by PREreview

Unbend: Correction of local beam-induced sample motion in cryo-EM images using a 3D spline model

1. Lingli Kong
2. Ximena Zottig
3. Johannes Elferich
4. Nikolaus Grigorieff

• Curated by eLife

  eLife Assessment

  This paper describes Unbend - a new method for measuring and correcting motions in cryo-EM images, with a particular emphasis on more challenging in situ samples such as lamellae and whole cells. The method, which fits a B-spline model using cross-correlation-based local patch alignment of micrograph frames, represents an important tool for the cryo-EM community. The authors elegantly use 2D template matching to provide convincing evidence that Unbend outperforms the previously reported method of Unblur by the same authors. Comparison to alternative programs for motion correction shows smaller gains, but with interesting differences between data sets.

Reviewed by eLife