Biophysics

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

Characterization of binding kinetics and intracellular signaling of new psychoactive substances targeting cannabinoid receptor using transition-based reweighting method

1. Soumajit Dutta
2. Diwakar Shukla

• Curated by eLife

  eLife Assessment

  A combination of molecular dynamics simulation and state-of-the-art statistical post-processing techniques provided valuable insight into GPCR-ligand dynamics. This manuscript provides solid evidence for differences in the binding/unbinding of classical cannabinoid drugs from new psychoactive substances. The results could aid in mitigating the public health threat these drugs pose.

Reviewed by eLife

Harnessing AlphaFold to reveal hERG channel conformational state secrets

1. Khoa Ngo
2. Pei-Chi Yang
3. Vladimir Yarov-Yarovoy
4. Colleen E Clancy
5. Igor Vorobyov

• Curated by eLife

  eLife Assessment

  This valuable study uses AlphaFold2 to guide the structural modelling of different states of the human voltage-gated potassium channel KV11.1, a key pharmacological drug target. Follow-up molecular dynamics and drug-docking simulations, combined with experimental characterization, offer convincing evidence supporting the models. The work shows potential for improving drug potency predictions in ion channel pharmacology.

Reviewed by eLife

Cellular coordination underpins rapid reversals in gliding filamentous cyanobacteria and its loss results in plectonemes

1. Jerko Rosko
2. Rebecca N Poon
3. Kelsey Cremin
4. Emanuele Locatelli
5. Mary Coates
6. Sarah JN Duxbury
7. Kieran Randall
8. Katie Croft
9. Chantal Valeriani
10. Marco Polin
11. Orkun S Soyer

• Curated by eLife

  eLife Assessment

  Using microscopy experiments and theoretical modelling, the authors present convincing evidence of cellular coordination in the gliding filamentous cyanobacterium Fluctiforma draycotensis. The results are fundamental for the understanding of cyanobacterial motility and the underlying molecular and mechanical pathways of cellular coordination.

Reviewed by eLife

Reconstitution of actomyosin networks in cell-sized liposomes reveals distinct mechanical roles of cytoskeletal organization in membrane shape remodeling

1. Makito Miyazaki
2. Fahmida Sultana Laboni
3. Taeyoon Kim

Reviewed by Arcadia Science

p53 isoforms have a high aggregation propensity, interact with chaperones and lack binding to p53 interaction partners

1. Anamari Brdar
2. Christian Osterburg
3. Philipp Münick
4. Anne Christin Machel
5. Rajeshwari Rathore
6. Susanne Osterburg
7. Büşra Yüksel
8. Birgit Schäfer
9. Kristina Desch
10. Julian D Langer
11. Ivan Dikic
12. Volker Dötsch

• Curated by eLife

  eLife Assessment

  This manuscript provides an important biochemical analysis of p53 isoforms, highlighting their aggregation propensity, interaction with chaperones, and dominant-negative effects on p53 family members. The authors have substantially strengthened the original manuscript by incorporating new mass spectrometry data and clarifying isoform-specific oligomerization behavior. Although the use of high expression levels limits direct physiological interpretation, the work is carefully framed as an investigation of protein misfolding and stability. Overall, this study offers convincing insights into p53 isoform biophysics with broad implications for cancer biology.

Reviewed by eLife