Biophysics

Molecular Drivers of RNA Phase Separation

1. V Ramachandran
2. DA Potoyan

Reviewed by PREreview

Genome-wide modeling of DNA replication in space and time confirms the emergence of replication specific patterns in vivo in eukaryotes

1. Dario D’Asaro
2. Jean-Michel Arbona
3. Vinciane Piveteau
4. Aurèle Piazza
5. Cédric Vaillant
6. Daniel Jost

Reviewed by Review Commons

Atypical collective oscillatory activity in cardiac tissue uncovered by optogenetics

1. Alexander S Teplenin
2. Nina N Kudryashova
3. Rupamanjari Majumder
4. Antoine AF de Vries
5. Alexander V Panfilov
6. Daniël Pijnappels
7. Tim De Coster

• Curated by eLife

  eLife Assessment

  This important work provides mechanistic insights into the development of cardiac arrhythmia and establishes a new experimental use case for optogenetics in studying cardiac electrophysiology. The agreement between computational models and experimental observations provides a convincing level of evidence that wave train-induced pacemaker activity can originate in continuously depolarized tissue, with the limitation that there may be differences between depolarization arising from constant optogenetic stimulation, as opposed to pathophysiological tissue depolarization. Future experiments in vivo and in other tissue preparations would extend the generality of these findings.

Reviewed by eLife

Conduction pathway for potassium through the E. coli pump KdpFABC

1. Adel Hussein
2. Xihui Zhang
3. Bjørn Panyella Pedersen
4. David L Stokes

• Curated by eLife

  eLife Assessment

  This valuable study provides new insights into the movement of ions through the bacterial pump KdpFABC, which regulates intracellular potassium concentration, by solving a 2.1 Å cryo-EM structure of the nanodisc-embedded active wild-type protein, and carrying out mutagenesis and activity assays. Although the structural data and analysis are solid, additional information about other structural classes identified in the EM data, as well as a discussion of relevant work done by others, would further strengthen these findings. The description of the activity assays is currently incomplete because more information is required to rigorously assess these experiments. This work will be of interest to the membrane transporter and channel communities and to microbiologists interested in osmoregulation and potassium homeostasis.

Reviewed by eLife

Dimerization and dynamics of angiotensin-I converting enzyme revealed by cryo-EM and MD simulations

1. Jordan M Mancl
2. Xiaoyang Wu
3. Minglei Zhao
4. Wei-Jen Tang

• Curated by eLife

  eLife Assessment

  This study shows, for the first time, the structure and snapshots of the dynamics of the full-length soluble Angiotensin-I converting enzyme dimer. The combination of structural and computational analyses provides compelling evidence that reveals the conformational dynamics of the complex and key regions mediating the conformational change. This fundamental work illustrates how conformational heterogeneity can be used to gain insights into protein function.

Reviewed by eLife

Emergence of specific binding and catalysis from a designed generalist binding protein

1. Yuda Chen
2. Sagar Bhattacharya
3. Lena Bergmann
4. Galen J. Correy
5. Sophia K. Tan
6. Kaipeng Hou
7. Justin Biel
8. Lei Lu
9. Ian Bakanas
10. Alexander N. Volkov
11. Ivan V. Korendovych
12. Nicholas F. Polizzi
13. James S. Fraser
14. William F. DeGrado

Reviewed by Arcadia Science

Expanding automated multiconformer ligand modeling to macrocycles and fragments

1. Jessica Flowers
2. Nathaniel Echols
3. Galen J Correy
4. Priyadarshini Jaishankar
5. Takaya Togo
6. Adam R Renslo
7. Henry van den Bedem
8. James S Fraser
9. Stephanie A Wankowicz

• Curated by eLife

  eLife Assessment

  The work presents a valuable extension of qFit-ligand, a computational method for modeling conformational heterogeneity of ligands in X-ray crystallography and cryo-EM density maps. The authors provide solid evidence of improved capabilities through careful validation against the previous version, particularly in expanding ligand sampling within conformational space. Such improvements suggest practical utility for challenging applications, including macrocyclic compound modeling and crystallographic drug fragment screening.

Reviewed by Arcadia Science, eLife

Impacts of structural properties of myosin II filaments on force generation

1. Shihang Ding
2. Pei-En Chou
3. Shinji Deguchi
4. Taeyoon Kim

• Curated by eLife

  eLife Assessment

  The authors present a useful agent-based model to study the tensile force generated by myosin mini-filaments in actin systems (bundles and networks); by numerically solving a mechanical model of myosin-II filaments, the authors provide insights into how the geometry of the molecular components and their elastic responses determine the force production. This work is of interest to biophysicists (in particular theoreticians) investigating force generation of motor molecules from a biomechanical engineering and physics perspective. The authors convincingly show that cooperative effects between multiple myosin filaments can enhance the total force generated, but not the efficiency of force generation (force per myosin) if passive cross-linkers are present. This work would benefit from a more extensive discussion of the physiological relevance of the results in view of the existing experimental literature, and how the principles that govern the behavior could be different for different motor proteins.

Reviewed by eLife

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. If robustly demonstrated, this work would open up new avenues for studying organelle membrane tension homeostasis. While the evidence is largely convincing and carefully quantified, a key limitation is the absence of data demonstrating that microinjection of cytoskeleton-depolymerizing drugs locally disrupts the target network.

Reviewed by eLife

SMC complex unidirectionally translocates DNA by coupling segment capture with an asymmetric kleisin path

1. Masataka Yamauchi
2. Giovanni B Brandani
3. Tsuyoshi Terakawa
4. Shoji Takada

• Curated by eLife

  eLife Assessment

  This important study presents a well-constructed multiscale simulation framework to investigate ATP-driven DNA translocation by prokaryotic SMC complexes, supporting a segment-capture mechanism. The strength of evidence is convincing, highlighting the necessity of a precise balance between electrostatic interactions and hydrogen bonding, as well as the critical role of kleisin asymmetry in ensuring unidirectional movement.

Reviewed by eLife