Biophysics

Structural Basis of Cold and Menthol Sensing by TRPM8

1. Hyuk-Joon Lee
2. Cheon-Gyu Park
3. Justin Gerald Fedor
4. Wyatt A. Peele
5. Mario J. Borgnia
6. Seok-Yong Lee

Reviewed by PREreview

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

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 David 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

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 A 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

Protein-induced membrane strain drives supercomplex formation

1. Maximilian C Pöverlein
2. Alexander Jussupow
3. Hyunho Kim
4. Ville RI Kaila

• Curated by eLife

  eLife Assessment

  In this important study, the authors conducted extensive atomistic and coarse-grained simulations as well as a lattice Monte Carlo analysis to probe the driving force and functional impact of supercomplex formation in the inner mitochondrial membrane. The study highlighted the major contribution from membrane mechanics to the supercomplex formation and revealed interesting differences in structural and dynamical features of the protein components upon complex formation. Upon revision, the analysis is considered solid, although the magnitude of estimated membrane deformation energies seem somewhat large. Overall, the study is thorough, creative and the impact on the field of bioenergetics is expected to be significant.

Reviewed by eLife