Biophysics

Evolution of a fuzzy ribonucleoprotein complex in viral assembly

1. Huaying Zhao
2. Tiansheng Li
3. Sergio A Hassan
4. Ai Nguyen
5. Siddhartha AK Datta
6. Guofeng Zhang
7. Camden Trent
8. Agata M Czaja
9. Di Wu
10. Maria A Aronova
11. Kin Kui Lai
12. Grzegorz Piszczek
13. Richard D Leapman
14. Jonathan W Yewdell
15. Peter Schuck

• Curated by eLife

  eLife Assessment

  This is a valuable study that combines biophysical and evolutionary approaches to understand why particular mutations in the SARS-CoV-2 protein N arose during the COVID-19 pandemic. The evidence is solid and supports the conclusions.

Reviewed by eLife

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 condensation or 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 combines theory and experiments and will help researchers in the field quantitatively interpret their findings. Given that phase separation of membrane bound molecules is becoming key in signaling, spanning from immune signaling to cell-cell adhesion, this work will be of broad interest for cell biologists and biophysicists.

Reviewed by eLife

Ω-Loop mutations control dynamics of the active site by modulating the hydrogen-bonding network in PDC-3 β-lactamase

1. Shuang Chen
2. Andrew R Mack
3. Andrea M Hujer
4. Christopher R Bethel
5. Robert A Bonomo
6. Shozeb Haider

• Curated by eLife

  eLife Assessment

  This manuscript uses adaptive-bandit simulations to describe the dynamics of the Pseudomonas-derived chephalosporinase PDC-3 β-lactamase and its mutants to better understand antibiotic resistance. The finding, that clinically observed mutations alter the flexibility of the Ω- and R2-loops, reshaping the cavity of the active site, is valuable to the field. The evidence is considered incomplete, however, with the need for analysis to demonstrate equilibrium weighting of adaptive trajectories and related measures of statistical significance.

Reviewed by eLife

Open Raman Microscopy (ORM): A Modular Hardware and Software Framework for Accessible Raman Imaging

1. Kevin T. Uning
2. Henry Brisebois
3. Conor C. Horgan
4. Magnus Jensen
5. Yue Yuan
6. Shiyue Liu
7. Elzbieta Stepula
8. Steven Vanuytsel
9. Vishal Kumar
10. Stephen Goldrick
11. Robert D. Knight
12. Martin A. B. Hedegaard
13. Michael B. Albro
14. Mads S. Bergholt
15. Michael R. Thomas

Reviewed by Arcadia Science

Fast MAS NMR Spectroscopy Can Identify G-Quartets and Double-Stranded Structures in Aggregates Formed by GGGGCC RNA Repeats

1. Sara Zager
2. Nataša Medved
3. Mirko Cevec
4. Urša Čerček
5. Boris Rogelj
6. Janez Plavec
7. Jaka Kragelj

Reviewed by Review Commons

Nucleosome wrapping energy in CpG islands and the role of epigenetic base modifications

1. Rasa Giniūnaitė
2. Rahul Sharma
3. John H Maddocks
4. Skirmantas Kriaučionis
5. Daiva Petkevičiūtė-Gerlach

• Curated by eLife

  eLife Assessment

  This valuable simulation study proposes a new coarse-grained model to explain the effects of CpG methylation on nucleosome wrapping energy. The model accurately reproduces the all-atom molecular dynamics simulation data, and the evidence to support the claims in the paper is solid. This work will be of interest to researchers working on gene regulation, mechanisms of DNA methylation and effects of DNA methylation on nucleosome positioning.

Reviewed by eLife

Dissecting Mechanisms of Ligand Binding and Conformational Changes in the Glutamine-Binding Protein

1. Zhongying Han
2. Sabrina Panhans
3. Sophie Brameyer
4. Ecenaz Bilgen
5. Marija Ram
6. Anna Herr
7. Alessandra Narducci
8. Michael Isselstein
9. Paul D Harris
10. Oliver Brix
11. Pazit Con
12. Kirsten Jung
13. Don C Lamb
14. Eitan Lerner
15. Douglas Griffith
16. Thomas R Weikl
17. Niels Zijlstra
18. Thorben Cordes

• Curated by eLife

  eLife Assessment

  This important study combines a comprehensive range of biophysical, kinetic, and thermodynamic techniques, together with high-quality experimental and computational analysis, to carry out a series of well-designed experiments to explore whether glutamine-binding protein binds glutamine via an induced fit or a conformational selection process. The evidence supporting the major conclusion of the work is compelling. The work will be of broad interest to biochemists and biophysicists.

Reviewed by eLife

Multiscale effects of perturbed translation dynamics inform antimalarial design

1. Leonie Anton
2. Wenjing Cheng
3. Meseret T. Haile
4. David W. Cobb
5. Xiyan Zhu
6. Leyan Han
7. Emerson Li
8. Anjali Nair
9. Carolyn L. Lee
10. Hangjun Ke
11. Guoan Zhang
12. Emma H. Doud
13. Chi-Min Ho

Reviewed by Rapid Reviews Infectious Diseases

Characterization and modulation of human insulin degrading enzyme conformational dynamics to control enzyme activity

1. Jordan M Mancl
2. Wenguang G Liang
3. Nicholas L Bayhi
4. Hui Wei
5. William Budell
6. Joshua H Mendez
7. Tobin R Sosnick
8. Bridget Carragher
9. Clinton S Potter
10. Wei-Jen Tang

• Curated by eLife

  eLife Assessment

  The manuscript by Mancl et al. provides important mechanistic insights into the conformational dynamics of Insulin Degrading Enzyme (IDE), a zinc metalloprotease involved in the clearance of amyloid peptides. In the revised version, the authors have substantially expanded their analysis by incorporating time-resolved cryo-EM and coarse-grained molecular dynamics simulations, which reveal an insulin-induced allosteric transition and transient β-sheet interactions underlying IDE's unfoldase activity. Supported by a convincing combination of cryo-EM, SEC-SAXS, enzymatic assays, and both all-atom and coarse-grained simulations, this work refines our understanding of IDE's functional cycle and offers a structural framework for developing substrate-selective modulators of M16 metalloproteases.

Reviewed by eLife

Multi-barrier unfolding of the double-knotted protein, TrmD–Tm1570, revealed by single-molecule force spectroscopy and molecular dynamics

1. Fernando Bruno da Silva
2. Szymon Niewieczerzal
3. Iwona Lewandowska
4. Mateusz Fortunka
5. Maciej Sikora
6. Laura-Marie Silbermann
7. Katarzyna Tych
8. Joanna I Sulkowska

• Curated by eLife

  eLife Assessment

  This study investigates the folding and unfolding behavior of the doubly knotted protein TrmD-Tm1570, providing insight into the molecular mechanisms underlying protein knotting. The findings reveal multiple unfolding pathways and suggest that the formation of double knots may require chaperone assistance, offering valuable insights into topologically complex proteins. The evidence is solid, supported by consistent agreement between simulation and experiment, though some aspects of the presentation and experimental scope could be clarified or expanded.

Reviewed by eLife