Biophysics

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

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

Non-Invasive Mechanical-Functional Analysis of Individual Liver Mitochondria by Atomic Force Microscopy

1. Ekaterina O. Zorikova
2. Sabita Chourasia
3. Irit Rosenhek-Goldian
4. Sidney R. Cohen
5. Semen V. Nesterov
6. Atan Gross

Reviewed by Review Commons

Unbend: Correction of local beam-induced sample motion in cryo-EM images using a 3D spline model

1. Lingli Kong
2. Ximena Zottig
3. Johannes Elferich
4. Nikolaus Grigorieff

• Curated by eLife

  eLife Assessment

  This paper describes Unbend - a new method for measuring and correcting motions in cryo-EM images, with a particular emphasis on more challenging in situ samples such as lamella and whole cells. The method, which fits a B-spline model using cross-correlation-based local patch alignment of micrograph frames, represents a valuable tool for the cryo-EM community. The authors elegantly use 2D template matching to provide solid evidence that Unbend outperforms the previously reported method of Unblur by the same authors. The paper would benefit from the inclusion of a similar analysis for established alternative methods, such as MotionCor2.

Reviewed by eLife

Conduction pathway for potassium through the Escherichia coli pump KdpFABC

1. Adel Hussein
2. Xihui Zhang
3. Bjørn P Pedersen
4. David L Stokes

• Curated by eLife

  eLife Assessment

  This manuscript revisits the well-studied KdpFABC potassium transport system from bacteria with a convincing set of new higher resolution structures, a protein expression strategy that permits purification of the active wildtype protein, and insight obtained from mutagenesis and activity assays. The thorough and thoughtful mechanistic analyses make this a valuable contribution to the membrane transport field.

Reviewed by eLife

Power-law decay of force on cell membrane tethers reflects long-ranged relaxation of membrane tension

1. Emeline Laborie
2. Andrew Callan-Jones

Reviewed by PREreview