Biophysics

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

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

Detergent-Triggered Membrane Remodelling Monitored via Intramembrane Fluorescence De-Quenching

1. Claudia M. F. Andrews
2. Christopher M. Hofmair
3. Lauryn Roberts
4. Emily James
5. Katie Morris
6. Kevin Kramm
7. Mark C. Leake
8. Yue Wang
9. Steven D. Quinn

Reviewed by preLights

Dynamic architecture of mycobacterial outer membranes revealed by all-atom simulations

1. Turner P Brown
2. Matthieu Chavent
3. Wonpil Im

• Curated by eLife

  eLife Assessment

  In their study, Brown et. al. provide an important advance in understanding the architecture of the mycobacterial outer membrane. Using all-atom simulations of model mycomembranes, the work reports compelling structural insights into how α-mycolic acids and outer leaflet lipids (PDIM and PAT) shape membrane organisation. The work revealed membrane heterogeneity with ordered inner leaflets and disordered outer leaflets that provide a molecular explanation for the resilience of the mycobacterial envelope.

Reviewed by eLife

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

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

• 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

Transforming a fragile protein helix into an ultrastable scaffold via a hierarchical AI and chemistry framework

1. Jun Qiu
2. Guojin Tang
3. Tianfu Feng
4. Bin Zheng
5. Yuanhao Liu
6. Peng Zheng

• Curated by eLife

  eLife Assessment

  This important work describes systematic computational and experimental approaches to turn a moderately stable α-helical bundle into a very stable fold. The authors advance our understanding of α-helix stabilization providing a convenient framework that has general implications for the protein design field. The main claims have convincing support through a sound methodology, with strong specific conclusions for designing mechanically, thermally, and chemically stable α-helical bundles.

Reviewed by eLife