Biophysics

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 Alexandra 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

Theory of non-dilute binding and surface phase separation applied to membrane-binding proteins

1. Xueping Zhao
2. Daxiao Sun
3. Giacomo Bartolucci
4. Anthony A Hyman
5. Alf Honigmann
6. Christoph A Weber

• Curated by eLife

  eLife Assessment

  This important study presents a compelling theoretical framework for understanding phase separation of membrane-bound proteins, with a focus on the organization of tight junction components. By incorporating non-dilute binding effects into thermodynamic models and validating the model's predictions with in vitro experiments on the tight junction protein ZO-1, the authors provide a quantitative tool that will be of interest for biologists interested in membrane-associated condensates. While further clarification of model assumptions and broader mechanistic context would strengthen the work even further, the combination of theory and experiment here is robust and a key advancement in the field.

Reviewed by eLife

Interpretable protein-DNA interactions captured by structure-sequence optimization

1. Yafan Zhang
2. Irene Silvernail
3. Zhuyang Lin
4. Xingcheng Lin

• Curated by eLife

  eLife Assessment

  This valuable work presents an interpretable protein-DNA Energy Associative (IDEA) model for predicting binding sites and affinities of DNA-binding proteins. While the method is convincing, it requires some adaptation for application to different proteins. The IDEA method is available and can be potentially used for predicting genome-wide protein-DNA binding sites.

Reviewed by eLife

Physical constraints and biological regulations underlie universal osmoresponses

1. Yiyang Ye
2. Qirun Wang
3. Jie Lin

• Curated by eLife

  eLife Assessment

  This manuscript develops a theoretical model of osmotic pressure adaptation in microbes by osmolyte production and wall synthesis. The prediction of a rapid increase in growth rate on osmotic shock is experimentally validated using fission yeast. By using phenomenological rules rather than detailed molecular mechanisms, the model can potentially apply to a wide range of microbes, providing important insights that would be of interest to the wider community studying the regulation of cell size and mechanics. The level of coarse-graining and the assumptions and limitations of the model have been well described, providing a convincing foundation for making predictions. However, further experimental work on the validity of the core assumptions across a range of microbial organisms is needed to assess the universality of the model.

Reviewed by eLife