Biophysics

Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2

1. Siyu Chen
2. Tamar Basiashvili
3. Joshua Hutchings
4. Marta Sanz Murillo
5. Amalia Villagran Suarez
6. Erica Xiong
7. Jaime Alegrio Louro
8. Andres E Leschziner
9. Elizabeth Villa

• Curated by eLife

  eLife Assessment

  In this manuscript, Chen et al. used cryo-ET and in vitro reconstituted system to demonstrate that the autoinhibited form of LRRK2 can also assemble into filaments on the microtubule surface, with a new interface involving the N-terminal repeats that were disordered in the previous active-LRRK2 filament structure. The structure obtained in this study is the highest resolution of LRRK2 filaments done by subtomogram averaging, representing a major technical advance compared to the previous paper from the same group. This is an important study, especially considering the pharmacological implications of the effect of inhibitors of the protein. The strengths of the data are convincing, but the study would be considerably strengthened if the authors explored the physiological significance of the new interfaces and the incomplete decoration of microtubules described here.

Reviewed by eLife

Balancing stability and flexibility when reshaping archaeal membranes

1. Miguel Amaral
2. Felix Frey
3. Xiuyun Jiang
4. Buzz Baum
5. Anđela Šarić

• Curated by eLife

  eLife Assessment

  This fundamental study characterizes the mechanics and stability of bolalipids from archaeal membranes using a minimalist, physics-based computational model. The authors present a robust mesoscale model of bolalipids-containing membranes, systematically evaluating it across diverse membrane configurations. The results are compelling, demonstrating that the incorporation of bolalipids and regular bilayer lipids in archaeal membranes significantly enhances membrane fluidity and structural stability.

Reviewed by eLife, Arcadia Science

Tension-Induced Stiffening of Cytoskeletal Components Regulates Cardiomyocyte Contractility

1. Mohammad Jafari
2. Sisir Datla
3. Elliot L. Elson
4. Brian E. Carlson
5. Tetsuro Wakatsuki
6. Farid Alisafaei

Reviewed by PREreview

Quantifying the shape of cells, from Minkowski tensors to p-atic orders

1. Lea Happel
2. Griseldis Oberschelp
3. Valeriia Grudtsyna
4. Harish P Jain
5. Rastko Sknepnek
6. Amin Doostmohammadi
7. Axel Voigt

• Curated by eLife

  eLife Assessment

  This important work describes a set of parameters that give a robust description of shape features of cells in tissues. The evidence for the usefulness of these parameters is solid. The work should be of interest for anybody analyzing epithelial dynamics, but more details about the analysis of experimental images are necessary and some streamlining of the text would increase the accessibility of the material for non-specialists.

Reviewed by eLife

Phase-Space Dynamics Reveal Structured and Chaotic Motility in Human Sperm via DTW Clustering

1. Athanasia Sergounioti
2. Efstathios Alonaris
3. Dimitrios Rigas

Reviewed by PREreview

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

Dimerization and dynamics of human 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 T. Biel
8. Lei Lu
9. Ian Bakanas
10. Jason E. Gestwicki
11. Alexander N. Volkov
12. Ivan V. Korendovych
13. Nicholas F. Polizzi
14. James S. Fraser
15. 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