Biophysics

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

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

Dynamic Architecture of Mycobacterial Outer Membranes Revealed by All-Atom Simulations

1. Turner P Brown
2. Matthieu Chavent
3. Wonpil Im

• Curated by eLife

  eLife Assessment

  In their study, Brown et. al. provide an important advance in understanding the architecture of the mycobacterial outer membrane. Using all-atom simulations of model mycomembranes, the work reports compelling structural insights into how α-mycolic acids and outer leaflet lipids (PDIM and PAT) shape membrane organisation. The work revealed membrane heterogeneity with ordered inner leaflets and disordered outer leaflets that provide a molecular explanation for the resilience of the mycobacterial envelope.

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

Longitudinal awake imaging of mouse deep brain microvasculature with super-resolution ultrasound localization microscopy

1. Yike Wang
2. Matthew R Lowerison
3. Zhe Huang
4. Qi You
5. Bing-Ze Lin
6. Daniel A Llano
7. Pengfei Song

• Curated by eLife

  eLife Assessment

  This study presents important methodologies for repeated brain ultrasound localization microscopy (ULM) in awake mice and a set of results indicating that wakefulness reduces vascularity and blood flow velocity. The data supporting these findings are solid. This study is relevant for scientists investigating vascular physiology in the brain.

Reviewed by eLife