Biophysics

Insights into substrate binding and utilization by hyaluronan synthase

1. Zachery Stephens
2. Julia Karasinska
3. Jochen Zimmer

• Curated by eLife

  eLife Assessment

  This study addresses a fundamental question in glycobiology by elucidating how a single-site processive enzyme orchestrates the alternating addition of sugars to synthesize complex polysaccharides such as hyaluronan. The findings are compelling, providing a clear mechanistic framework supported by strong experimental validation. Major strengths include the integration of high-resolution structural data with rigorous biochemical analyses, resulting in a well-supported model of hyaluronan assembly.

Reviewed by eLife

Pulsed laser lensing for phase modulation in electron microscopy

1. Daniel X Du
2. Adam C Bartnik
3. Cameron JR Duncan
4. Usama Choudhry
5. Tanya Tabachnik
6. Chaim Sallah
7. Yuki Ogawa
8. Ebrahim Najafi
9. Ding-Shyue Yang
10. Jared M Maxson
11. Anthony WP Fitzpatrick

• Curated by eLife

  eLife Assessment

  This important study introduces a pulsed laser phase plate that generates stable phase contrast in electron microscopy, offering a practical alternative to continuous-wave designs that suffer from optical instabilities and diffraction artifacts. The experimental results demonstrate a controllable and stable electron phase shift, and the evidence supporting the feasibility of this approach for phase-contrast electron microscopy is convincing. Clarifying the agreement between experiment and theory and further elaborating on possible applications would strengthen the manuscript.

Reviewed by eLife

Unraveling the Molecular Mechanisms of ABHD5 Membrane Targeting

1. Amit Kumar
2. Matthew Sanders
3. Huamei Zhang
4. Li Zhou
5. Shahnaz Parveen
6. Miriam C Jensen
7. Thomas JD Jørgensen
8. Christopher V Kelly
9. James G Granneman
10. Yu-ming M Huang

• Curated by eLife

  eLife Assessment

  This study makes a valuable contribution to our understanding of how the lipase regulator ABHD5 may control lipase activity through interactions with lipid droplets and cellular membranes. By combining multiscale molecular dynamics simulations with experimental approaches, the authors provide novel molecular insights into this membrane-protein interaction and present evidence suggesting that the regulatory mechanism depends on protein conformational changes and local membrane remodeling. While much of the evidence supporting the main conclusions is convincing, several aspects of the analysis, interpretation, and discussion remain incomplete. Overall, this work will be of interest to structural and molecular biologists working on lipid metabolism and membrane biophysics.

Reviewed by eLife

Conformational Changes of the ABC Transporter BmrA Depend on Membrane Curvature

1. Alicia Damm
2. Kemil Belhadji
3. Raj Kumar Sadhu
4. Su-Jin Paik
5. Aurélie Di-Cicco
6. John Manzi
7. Michele Castellana
8. Raju Regmi
9. Emmanuel Margeat
10. Maxime Dahan
11. Pierre Sens
12. Daniel Lévy
13. Patricia Bassereau

• Curated by eLife

  eLife Assessment

  This valuable study investigates whether the activity of an ABC transporter, BmrA, can be modulated by mechanical stimuli. The authors develop a single-molecule experimental system to address this question, although aspects of the methodological framework are incomplete. This work also develops a convincing theoretical model to explain the effect of membrane curvature on the conformational transitions observed during the activity cycle of this membrane protein. This study is of interest to the fields of membrane biophysics and membrane transport.

Reviewed by eLife

Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion

1. Irène Nagle
2. Margherita Tavasso
3. Ankur D. Bordoloi
4. Iain A.A. Muntz
5. Gijsje H. Koenderink
6. Pouyan E. Boukany

Reviewed by PREreview

Stall force measurement of the kinesin-3 motor KIF1A using a programmable DNA origami nanospring

1. Nobumichi Takamatsu
2. Hiroko Furumoto
3. Takayuki Ariga
4. Mitsuhiro Iwaki
5. Kumiko Hayashi

• Curated by eLife

  eLife Assessment

  Optical tweezers have been instrumental to the determination of mechanical parameters of molecular motors. This study by Takamatsu et al. reports key mechanical parameters of kinesin KIF1A using fluorescence microscopy, wherein the motor is tethered to a DNA nanospring, without the use of an optical trapping apparatus, which represents an exciting development. The approach and the findings reported change current thinking about KIF1A‑mediated transport, with potential implications for understanding human disease. The findings are important and the strength of the evidence is compelling.

Reviewed by eLife

Active regulation of the epidermal growth factor receptor by the membrane bilayer

1. Shwetha Srinivasan
2. Xingcheng Lin
3. Xuyan Chen
4. Raju Regmi
5. Bin Zhang
6. Gabriela S Schlau-Cohen

• Curated by eLife

  eLife Assessment

  The authors describe an interesting approach to studying the dynamics and function of membrane proteins in different lipid environments. The fundamental findings have theoretical and practical implications beyond the study of EGFR to all membrane signalling proteins. The evidence supporting the conclusions is compelling, based on the use of a nanodisk system to study membrane proteins in vitro, combined with state-of-the-art single-molecule FRET. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife

Cluster size determines internal structure of transcription factories in human cells

1. Massimiliano Semeraro
2. Giuseppe Negro
3. Giada Forte
4. Antonio Suma
5. Giuseppe Gonnella
6. Peter Cook
7. Davide Marenduzzo

• Curated by eLife

  eLife Assessment

  This is a valuable polymer model that provides insight into the origin of macromolecular mixed and demixed states within transcription clusters. The simulations are well performed and clearly presented in the context of existing experimental datasets. This compelling study will be of interest to those studying gene expression in the context of chromatin.

Reviewed by eLife

Effects of residue substitutions on the cellular abundance of proteins

1. Thea K Schulze
2. Kresten Lindorff-Larsen

• Curated by eLife

  eLife Assessment

  This valuable study presents a thorough analysis of protein abundance changes caused by amino acid substitutions, using structural context to improve predictive accuracy. By deriving substitution response matrices based on solvent accessibility, the authors demonstrate that simple structural features can predict abundance effects with accuracy comparable to complex methods such as free energy calculations. The strength of the evidence is convincing, supported by robust experimental design and comprehensive analyses.

Reviewed by eLife, PREreview

Allosteric effects of the coupling cation in melibiose transporter MelB

1. Parameswaran Hariharan
2. Yuqi Shi
3. Amirhossein Bakhtiiari
4. Ruibin Liang
5. Rosa Viner
6. Lan Guan

• Curated by eLife

  eLife Assessment

  This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this convincing study improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes binding and transport assays, as well as HDX-MS and molecular dynamics simulations to further understand the positive cooperativity between sugar and the co-transported sodium cation. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

Reviewed by eLife