Biophysics

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

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

DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2 and -3

1. Crystal R Noell
2. Tzu-Chen Ma
3. Rui Jiang
4. Scott A McKinley
5. William O Hancock

• Curated by eLife

  eLife Assessment

  The use of DNA tethers is an important advance for studying how motor proteins respond to load. The authors use a convincing methodology to investigate the detachment and reattachment kinetics of kinesin-1, 2, and 3 motors against loads oriented parallel to the microtubule. As the manuscript stands, the conclusions drawn from the experiments, as well as the overall interpretation of the results, are incompletely supported by the presented data, and the novelty over previous reports appears less clear.

Reviewed by eLife

Enhanced Processivity and Collective Force Production of Kinesins at Low Radial Forces

1. Andrew M Hensley
2. Ahmet Yildiz

• Curated by eLife

  eLife Assessment

  The manuscript by Hensley and Yildez studies the mechanical behavior of kinesin under conditions where the z-component of the applied force is minimized. The important study shows that much of the mechanical information gleaned from the traditional "one bead" with attached kinesin approach was probably profoundly influenced by the direction of the applied force. The data are convincing, but in some cases the amount of data collected appears to be smaller than optimal.

Reviewed by eLife