Biophysics

Functionally coupled ion channels begin co-assembling at the start of their synthesis

1. Roya Pournejati
2. Jessica M Huang
3. Michael Ma
4. Claudia M Moreno
5. Oscar Vivas

• Curated by eLife

  eLife Assessment

  This fundamental manuscript provides compelling evidence that BK and CaV1.3 channels can co-localize as ensembles early in the biosynthetic pathway, including within the ER and Golgi. The findings, supported by a range of imaging and proximity assays, offer insights into channel organization in both heterologous and endogenous systems. The data substantiate the central claims, while highlighting intriguing mechanistic questions for future studies: the determinants of mRNA co-localization, the temporal dynamics of ensemble trafficking, and the physiological implications of pre-assembly for channel function at the plasma membrane.

Reviewed by eLife

Lenacapavir-induced Lattice Hyperstabilization is Central to HIV-1 Capsid Failure at the Nuclear Pore Complex and in the Cytoplasm

1. Arpa Hudait
2. Ryan C Burdick
3. Ellie K Bare
4. Vinay K Pathak
5. Gregory A Voth

• Curated by eLife

  eLife Assessment

  This study investigates how the HIV inhibitor lenacapavir influences capsid mechanics and interactions with the nuclear pore complex. It provides important insights into how drug-induced hyperstabilization of the viral shell can compromise its structural integrity during nuclear entry. While the modeling is technically sophisticated and the results are promising, some mechanistic interpretations rely on assumptions embedded in the simulations, leaving parts of the evidence incomplete.

Reviewed by eLife

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 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

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 Kriaucionis
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