Biophysics

Ligand-coupled conformational changes in a cyclic nucleotide-gated ion channel revealed by time-resolved transition metal ion FRET

1. Pierce Eggan
2. Sharona E Gordon
3. William N Zagotta

• Curated by eLife

  eLife Assessment

  This valuable study uses fluorescence lifetime imaging and steady-state and time-resolved transition metal ion FRET to characterize conformational transitions in the isolated cyclic nucleotide binding domain of a bacterial CNG channel. The data are compelling and support the authors' conclusions. The results advance the understanding of allosteric mechanisms in CNBD channels and have theoretical and practical implications for other studies of protein allostery. A limitation is that only the cytosolic fragments of the channel were studied.

Reviewed by eLife

FLIMPA: A Versatile Software for Fluorescence Lifetime Imaging Microscopy Phasor Analysis

1. Sofia Kapsiani
2. Nino F. Läubli
3. Edward N. Ward
4. Mona Shehata
5. Clemens F. Kaminski
6. Gabriele S. Kaminski Schierle

Reviewed by Arcadia Science

Biophysical limits of ultrafast cellular motility

1. Ray Chang
2. Manu Prakash

Reviewed by Arcadia Science

The interplay between biomolecular assembly and phase separation

1. Giacomo Bartolucci
2. Ivar S Haugerud
3. Thomas CT Michaels
4. Christoph A Weber

• Curated by eLife

  eLife Assessment

  The authors present an important theoretical framework that describes the interplay between liquid-liquid phase separation and protein aggregation within a mean-field model. This work will be of high interest to the biophysics and molecular biology communities, as it will help understand and analyse assembly within biomolecular condensates in cells or in-vitro. Major strengths of this convincing work are the consideration of aggregates with various dimensionality and the possibility for protein gelation.

Reviewed by eLife

Phosphorylation regulated conformational diversity and topological dynamics of an intrinsically disordered nuclear receptor

1. Vasily Akulov
2. Alba Jiménez Panizo
3. Eva Estébanez-Perpiñá
4. John van Noort
5. Alireza Mashaghi

Reviewed by Arcadia Science

An integrated machine learning approach delineates an entropic expansion mechanism for the binding of a small molecule to α-synuclein

1. Sneha Menon
2. Subinoy Adhikari
3. Jagannath Mondal

• Curated by eLife

  eLife Assessment

  This study describes the application of machine learning and Markov state models to characterize the binding mechanism of alpha-Synuclein to the small molecule Fasudil. The results suggest that entropic expansion can explain such binding. However, the simulations and analyses in their present form are inadequate.

Reviewed by eLife

Direct and indirect salt effects on homotypic phase separation

1. Matt MacAinsh
2. Souvik Dey
3. Huan-Xiang Zhou

• Curated by eLife

  eLife Assessment

  In this potentially important study, the authors conducted atomistic simulations to probe the salt-dependent phase separation of the low-complexity domain of hnRN-PA1 (A1-LCD). The authors have identified both direct and indirect mechanisms of salt modulation, provided explanations for four distinct classes of salt dependence, and proposed a model for predicting protein properties from amino acid composition. There is a range of opinions regarding the strength of evidence, with some considering the evidence as incomplete due to the limitations in the length and statistical errors of the computationally intense atomistic MD simulations.

Reviewed by eLife

TMEM16 and OSCA/TMEM63 proteins share a conserved potential to permeate ions and phospholipids

1. Augustus J Lowry
2. Pengfei Liang
3. Mo Song
4. Yuichun Wan
5. Zhen-Ming Pei
6. Huanghe Yang
7. Yang Zhang

• Curated by eLife

  eLife Assessment

  This important study advances our understanding of the mechanisms controlling lipid flux and ion permeation in the TMEM16 and OSCA/TMEM63 family channels. The study provides compelling new evidence indicating that side chains along the TM4/6 interface play a key role in gating lipid and ion fluxes in these channels. The authors suggest that the transmembrane channel/scramblase family proteins may have originally functioned as scramblases but lost this capacity over evolution.

Reviewed by eLife

HIV integrase compacts viral DNA into biphasic condensates

1. Pauline J Kolbeck
2. Marjolein de Jager
3. Margherita Gallano
4. Tine Brouns
5. Ben Bekaert
6. Wout Frederickx
7. Sebastian F Konrad
8. Siska Van Belle
9. Frauke Christ
10. Steven De Feyter
11. Zeger Debyser
12. Laura Filion
13. Jan Lipfert
14. Willem Vanderlinden

• Curated by eLife

  eLife Assessment

  The manuscript by Kolbeck and co-workers is an important contribution to understanding the physical mechanism that controls a key step in the retroviral infectious cycle. The authors employ a wide range of experimental techniques, complemented with Montecarlo simulations, that result in convincing evidence of compaction of HIV DNA by the viral integrase. This manuscript would benefit from in-depth discussion and analysis of the biophysical implications of the results.

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 potentially 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 importance of membrane mechanics to the supercomplex formation and revealed differences in structural and dynamical features of the protein components upon complex formation. In its current form, the analysis is considered incomplete, especially concerning the contributions of membrane mechanics and allosteric coupling of key regions.

Reviewed by eLife