Biophysics

Determinants of sugar-induced influx in the mammalian fructose transporter GLUT5

1. Sarah E McComas
2. Tom Reichenbach
3. Darko Mitrovic
4. Claudia Alleva
5. Marta Bonaccorsi
6. Lucie Delemotte
7. David Drew

• Curated by eLife

  eLife assessment

  The current manuscript investigates the energy landscape of the mammalian sugar porter GLUT5 using enhanced molecular dynamics simulations and biochemical assays. The approach generates important insights into the mechanism of GLUT5 conformational change, and into mechanistic diversity among the GLUT sugar porters more generally. The overall strategy is solid, but without an additional error analysis, the computational components remain incomplete. These findings will be of interest to the transporter and membrane biology communities.

Reviewed by eLife

Interplay between VSD, pore, and membrane lipids in electromechanical coupling in HCN channels

1. Ahmad Elbahnsi
2. John Cowgill
3. Verena Burtscher
4. Linda Wedemann
5. Luise Zeckey
6. Baron Chanda
7. Lucie Delemotte

• Curated by eLife

  eLife assessment

  Hyperpolarised-activated and Cyclic Nucleotide-gated (HCN) channels are the only mammalian channels to open under hyperpolarisation, being important for their roles in cardiac and neuronal cells. The authors of this study use atomistic simulations to enforce changing interaction distances that have been identified from a cryoEM structure and a homology model based on the hERG channel. The simulations suggest state-dependent interactions involving pore and voltage sensor helices, as well as with lipids, leading the authors to propose a domino-like mechanism of activation. These findings will be of considerable interest to the ion channel community.

Reviewed by eLife

Direct observation of coordinated assembly of individual native centromeric nucleosomes

1. Andrew R Popchock
2. Joshua D Larson
3. Julien Dubrulle
4. Charles L Asbury
5. Sue Biggins

Reviewed by Review Commons

Global alignment and local curvature of microtubules in mouse fibroblasts are robust against perturbations of vimentin and actin

1. Anna Blob
2. David Ventzke
3. Ulrike Rölleke
4. Giacomo Nies
5. Axel Munk
6. Laura Schaedel
7. Sarah Köster

Reviewed by Arcadia Science

Reconstructing the transport cycle in the sugar porter superfamily using coevolution-powered machine learning

1. Darko Mitrovic
2. Sarah E McComas
3. Claudia Alleva
4. Marta Bonaccorsi
5. David Drew
6. Lucie Delemotte

• Curated by eLife

  eLife assessment

  This potentially important work proposes a novel approach, based on co-evolution analysis, machine-learning protocols and molecular dynamics simulations, to predict structures and energetics of the main states of the alternating access cycle of a family of membrane transporters, the sugar porters. The approach is compelling, especially the application of co-evolution and Alphafold to generate highly accurate models in different conformational states of a given protein, but the work is currently incomplete due to shortcomings in the calculation of the energy landscape. With this aspect strengthened, the manuscript will be of interest to the transporter and computational modeling communities.

Reviewed by eLife

Protein compactness and interaction valency define the architecture of a biomolecular condensate across scales

1. Anton A Polyansky
2. Laura D Gallego
3. Roman G Efremov
4. Alwin Köhler
5. Bojan Zagrovic

• Curated by eLife

  eLife assessment

  This study reports a joint experimental and computational investigation of the structural features of biomolecular condensates formed by a specific intrinsically disordered protein. The authors also adapt emerging rules to discuss and physico-chemical determinants of these structures of condensates. Specifically, the authors adapt the analysis of fractal structures, co-opted from the field of colloidal chemistry / physics, and generate important insights regarding the network-like organization of disordered proteins within in silico facsimiles of condensates. The usage of these analyses in the context of studying all atom models for multi-chain assemblies intended to mimic the internal organization of condensates is very interesting. The work is of relevance to cell biology and structural biology.

Reviewed by eLife

Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins

1. Seoyoon Kim
2. Daehyo Lee
3. WC Bhashini Wijesinghe
4. Duyoung Min

• Curated by eLife

  eLife assessment

  This work presents an important methodological advance for single-molecule force spectroscopy of membrane proteins providing a new robust design of the linkage between a target single molecule and solid support. The data provide compelling evidence of the improved mechanical stability of the pulling system. Allowing more statistically reliable force measurements of biomolecules, this method may be broadly applicable in the field of single-molecule biophysics.

Reviewed by eLife

Structural and mechanistic insights into the MCM8/9 helicase complex

1. Zhuangfeng Weng
2. Jiefu Zheng
3. Yiyi Zhou
4. Zuer Lu
5. Yixi Wu
6. Dongyi Xu
7. Huanhuan Li
8. Huanhuan Liang
9. Yingfang Liu

• Curated by eLife

  eLife assessment

  This paper presents important findings on the hexametric structure of MCM8/9, which potentially explain its role as a DNA helicase in homologous recombination. This solid work will be of interest to biologists studying DNA transactions.

Reviewed by eLife

Cannabidiol sensitizes TRPV2 channels to activation by 2-APB

1. Aaron Gochman
2. Xiao-Feng Tan
3. Chanhyung Bae
4. Helen Chen
5. Kenton J Swartz
6. Andres Jara-Oseguera

• Curated by eLife

  eLife assessment

  This is an important report on the discovery of a strong sensitizing effect of cannabidiol on the activation of TRPV2 channels by 2-APB. The conclusions are convincingly supported by solid electrophysiological recordings and cryo-EM structures, but identification of a clear molecular mechanism will require additional structural work. The paper will be of interest to the ion channel research community.

Reviewed by eLife

Structure of the HIV immature lattice allows for essential lattice remodeling within budded virions

1. Sikao Guo
2. Ipsita Saha
3. Saveez Saffarian
4. Margaret E Johnson

• Curated by eLife

  eLife assessment

  This is a valuable study, carried out in a solid and comprehensive manner. The results advance the understanding of one of the steps of the HIV life cycle, via a better description of the mechanisms underlying Gag-Pol dimerization.

Reviewed by eLife