Biophysics

Domain Coupling in Allosteric Regulation of SthK Measured Using Time-Resolved Transition Metal Ion FRET

1. Pierce Eggan
2. Sharona E Gordon
3. William N Zagotta

• Curated by eLife

  eLife Assessment

  This valuable study employs transition-metal FRET (tmFRET) and time-correlated single-photon counting to investigate allosteric conformational changes in both isolated cyclic nucleotide-binding domains (CNBDs) and full-length bacterial CNG channels, demonstrating that transmembrane domains stabilize CNBDs in their active state. By comparing isolated CNBD constructs with full-length channels, the authors reveal how allosteric networks couple domain movements to gating energetics, providing insights into ion channel regulation mechanisms. The rigorous methodology and compelling quantitative analysis establish a framework for applying tmFRET to study conformational dynamics in diverse protein systems.

Reviewed by eLife

The cytoplasm of living cells can sustain transient and steady intracellular pressure gradients

1. Majid Malboubi
2. Mohammad Hadi Esteki
3. Lulu IT Korsak
4. Ryan J Petrie
5. Emad Moeendarbary
6. Guillaume Charras

• Curated by eLife

  eLife Assessment

  This important study combines imaginative experiments to demonstrate the relevance of poroelasticity in the mechanical properties of cells across physiologically relevant time and length scales. Through innovative experiments and a finite element model, the authors present solid evidence that cytosolic flows and pressure gradients can persist in cells with permeable membranes, generating spatially segregated influx and outflux zones. These findings will be of interest to the cell biology and biophysics communities. Nevertheless, a more in depth discussion of why other possible explanations for the long time scales associated to mechanical propagation are less effective could further strengthen their message.

Reviewed by eLife

The C-terminus of the multi-drug efflux pump EmrE prevents proton leak by gating transport

1. Merissa Brousseau
2. Da Teng
3. Nathan E Thomas
4. Gregory A Voth
5. Katherine A Henzler-Wildman

• Curated by eLife

  eLife Assessment

  This study provides a fundamental analysis of the EmrE efflux pump, highlighting the role of the C-terminal domain in influencing uncoupled proton leak. The integration of biophysical techniques with molecular dynamics simulations offers solid support for the key findings and adds substantial evidence toward a definitive understanding of EmrE transport mechanism.

Reviewed by eLife

Polyphosphate discriminates protein conformational ensembles more efficiently than DNA promoting diverse assembly and maturation behaviors

1. Saloni Goyal
2. Divya Rajendran
3. Anup Kumar Mani
4. Athi N Naganathan

• Curated by eLife

  eLife Assessment

  This manuscript offers important insights into how polyphosphate (polyP) influences protein phase separation differently from DNA. The authors present compelling evidence that polyP distinguishes among protein conformational ensembles, leading to divergent condensate maturation behaviors that include unfolding and polyproline II formation. In response to reviewer feedback, the authors addressed key concerns by incorporating charge-equivalent DNA controls and extending structural analysis to FruR variants, further reinforcing the polymer-specific effects of polyP. While some discrepancies between protein systems remain unresolved, the study enhances our understanding of how biopolymers influence protein assembly and conformational transitions.

Reviewed by eLife

Altair-LSFM: A High-Resolution, Easy-to-Build Light-Sheet Microscope for Sub-Cellular Imaging

1. John Haug
2. Seweryn Gałecki
3. Kevin M Dean

• Curated by eLife

  eLife Assessment

  This useful study presents Altair-LSFM, a solid and well-documented implementation of a light-sheet fluorescence microscope (LSFM) designed for accessibility and cost reduction. While the approach offers strengths such as the use of custom-machined baseplates and detailed assembly instructions, its overall impact is limited by the lack of live-cell imaging capabilities and the absence of a clear, quantitative comparison to existing LSFM platforms. As such, although technically competent, the broader utility and uptake of this system by the community may be limited.

Reviewed by eLife

PRC1 resists microtubule sliding in two distinct resistive modes due to variations in the separation between overlapping microtubules

1. Daniel Steckhahn
2. Shane A. Fiorenza
3. Ellinor Tai
4. Scott Forth
5. Peter R. Kramer
6. Meredith Betterton

Reviewed by Review Commons

Oligomerization enables the selective targeting of intrinsically disordered regions by small molecules

1. Stasė Bielskutė
2. Borja Mateos
3. Muhammad Awawdy
4. Carla Garcia-Cabau
5. Henri Niskanen
6. Carolina Sánchez-Zarzalejo
7. Lorenzo Bracaglia
8. Roberta Pierattelli
9. Isabella C. Felli
10. Marta Frigolé-Vivas
11. Jesús García
12. Antoni Riera
13. Denes Hnisz
14. Xavier Salvatella

Reviewed by PREreview

Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes

1. Upasana L Mallimadugula
2. Matthew A Cruz
3. Neha Vithani
4. Maxwell I Zimmerman
5. Gregory R Bowman

• Curated by eLife

  eLife Assessment

  This study provides important insights into how cryptic pockets play a role in shaping binding preferences of protein-nucleic acid interactions. By combining biochemical assays and state-of-the-art molecular dynamics simulations, mechanism underlying viral protein 35 (VP35) homologs to bind the backbone of double stranded RNA is presented. The evidence is compelling for molecular determinants that suggest two different dsRNA binding modes for VP35 and also underscores the evolutionary importance of these pockets.

Reviewed by eLife

Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove

1. Christina A Stephens
2. Niek van Hilten
3. Lisa Zheng
4. Michael Grabe

• Curated by eLife

  eLife Assessment

  This important study provides information on the TMEM16 family of membrane proteins, which play roles in lipid scrambling and ion transport. By simulating 27 structures representing five distinct family members, the authors captured hundreds of lipid scrambling events, offering insights into the mechanisms of lipid translocation and the specific protein regions involved in these processes. While the data on comparison of scrambling competence is compelling, the evidence for outside-the-groove scramblase activity without experimental validation is missing and is based on a limited set of observed events.

Reviewed by eLife

Swirling motion of breast cancer cells radially aligns collagen fibers to enable collective invasion

1. Aashrith Saraswathibhatla
2. Md Foysal Rabbi
3. Sushama Varma
4. Vasudha Srivastava
5. Olga Ilina
6. Naomi Hassan Kahtan Alyafei
7. Louis Hodgson
8. Zev Gartner
9. Peter Friedl
10. Robert West
11. Taeyoon Kim
12. Ovijit Chaudhuri

Reviewed by preLights