Biophysics

Modulation of α-synuclein aggregation amid diverse environmental perturbation

1. Abdul Wasim
2. Sneha Menon
3. Jagannath Mondal

• Curated by eLife

  eLife assessment

  This study provides important biophysical insights into the molecular mechanism underlying the association of alpha-synuclein chains, which is essential for understanding the pathogenesis of Parkinson's disease. The data analysis is solid, and the methodology can help investigate other molecular processes involving intrinsically disordered proteins.

Reviewed by eLife

Differential conformational dynamics in two type-A RNA-binding domains drive the double-stranded RNA recognition and binding

1. Firdousi Parvez
2. Devika Sangpal
3. Harshad Paithankar
4. Zainab Amin
5. Jeetender Chugh

• Curated by eLife

  eLife assessment

  This study presents a useful comparison of the dynamic properties of two RNA-binding domains. The data collection and analysis are solid, making excellent use of a suite of NMR experiments and ITC data. Nonetheless, reported evidence was found to only partially support the proposed connection between the backbone dynamics of the tandem domains and their RNA binding activity. This work will be of interest to biophysicists working on RNA-binding proteins.

Reviewed by eLife

OpenNucleome for high-resolution nuclear structural and dynamical modeling

1. Zhuohan Lao
2. Kartik D Kamat
3. Zhongling Jiang
4. Bin Zhang

• Curated by eLife

  eLife assessment

  This important work significantly advances the field of computational modelling of genome organisation through the development of OpenNucleome. The evidence supporting the tool's effectiveness is compelling, as the authors compare their predictions with experimental data. It is anticipated that OpenNucleome will attract significant interest from the biophysics and genomics communities.

Reviewed by eLife

Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts

1. Po-Lin Chiu
2. Juan D Orjuela
3. Bert L de Groot
4. Camilo Aponte Santamaría
5. Thomas Walz

• Curated by eLife

  eLife assessment

  This manuscript aims to unravel the contribution of cholesterol to aquaporin-0 (AQP0) tetramer array formation within lens membranes. Compelling electron crystallography data are combined with solid molecular dynamics experiments to identify a specific cholesterol binding site of significance to protein clustering within lipid rafts. The important work advances our understanding of membrane biology and will be of broad interest to membrane transport biologists, biochemists, and structural biologists.

Reviewed by eLife

A complete map of specificity encoding for a partially fuzzy protein interaction

1. Taraneh Zarin
2. Ben Lehner

Reviewed by PREreview

Cryo-EM structure and biochemical analysis of human chemokine receptor CCR8

1. Qi Peng
2. Haihai Jiang
3. Xinyu Cheng
4. Na Wang
5. Sili Zhou
6. Yuting Zhang
7. Tingting Yang
8. Yixiang Chen
9. Wei Zhang
10. Sijia Lv
11. Weiwei Nan
12. JianFei Wang
13. Guo-Huang Fan
14. Jian Li
15. Jin Zhang

Reviewed by PREreview

The mechanism of mammalian proton-coupled peptide transporters

1. Simon M Lichtinger
2. Joanne L Parker
3. Simon Newstead
4. Philip C Biggin

• Curated by eLife

  eLife assessment

  This study provides important insight into the mechanisms of proton-coupled oligopeptide transporters. It uses enhanced-sampling molecular dynamics (MD), backed by cell-based assays, revealing the importance of protonation of selected residues for PepT2 function. The simulation approaches are convincing, using long MD simulations, constant-pH MD and free energy calculations. Overall, the work has led to findings that will appeal to structural biologists, biochemists, and biophysicists studying membrane transporters.

Reviewed by eLife

Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration

1. Debabrata Dey
2. Shir Marciano
3. Anna Poryvai
4. Ondřej Groborz
5. Lucie Wohlrábová
6. Tomás Slanina
7. Gideon Schreiber

• Curated by eLife

  eLife assessment

  This is a valuable study on the diffusion rates of drug molecules in human-derived cells, highlighting that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The correlation between pKa and intracellular diffusion is solid and well-supported, but the study would benefit from a more rigorous statistical treatment and a balanced comparison across different types of compounds. Despite these limitations, the findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

Reviewed by eLife

Insulator-based dielectrophoresis-assisted separation of insulin secretory vesicles

1. Mahta Barekatain
2. Yameng Liu
3. Ashley Archambeau
4. Vadim Cherezov
5. Scott Fraser
6. Kate L White
7. Mark A Hayes

• Curated by eLife

  eLife assessment

  This paper presents a new method for separating organelles in an unbiased way. The method is applied to the separation of distinct subpopulations of insulin vesicles. There are concerns around whether the vesicles measured are in fact insulin vesicles and whether the observed changes in vesicle populations upon glucose stimulation are biologically meaningful, and thus it is difficult to assess at this stage how well the technique performs. This paper is likely to be of wide interest to cell biologists studying a variety of compartments, as well as to researchers in the beta cell field.

Reviewed by eLife

Wide Transition-State Ensemble as Key Component for Enzyme Catalysis

1. Gabriel Ernesto Jara
2. Francesco Pontiggia
3. Renee Otten
4. Roman V. Agafonov
5. Marcelo A. Martí
6. Dorothee Kern

• Curated by eLife

  eLife assessment

  In this potentially important study, the authors report results of QM/MM simulations and kinetic measurements for the phosphoryl-transfer step in adenylate kinase. The results point to the mechanistic proposal that the transition state ensemble is broader in the most efficient form of the enzyme (i.e., in the presence of Mg2+ in the active site) and thus a different activation entropy. With a broad set of computations and experimental analyses, the level of evidence is considered solid by some reviewers. On the other hand, there remain limitations in the computational analyses, especially regarding free energy profiles using different methodologies and the activation entropy, leading some reviewers to the evaluation that the level of evidence is incomplete.

Reviewed by eLife