Biochemistry

The Structural Dynamics of IRE1 and its Interaction with Unfolded Peptides

1. Elena Spinetti
2. G Elif Karagöz
3. Roberto Covino

• Curated by eLife

  eLife Assessment

  In this important study, the authors conducted atomistic molecular dynamics simulations to probe the interactions between IRE and unfolded peptides. The results help reconcile contradicting experimental findings in the literature and offer mechanistic insights into the activation of the unfolded protein response. The atomistic molecular dynamics simulations performed are solid, leading to convincing conclusions that are partly supported by experimental validations. The use of unbiased molecular dynamics simulations, while appropriate for the current system due to its complexity, limits the time scale of events that can be observed and therefore the proposed mechanism of recognition merits further confirmation by future studies.

Reviewed by eLife

A simplified and highly efficient cell-free protein synthesis system for prokaryotes

1. Xianshengjie Lang
2. Changbin Zhang
3. Jingxuan Lin
4. Zhe Zhang
5. Wenfei Li

• Curated by eLife

  eLife Assessment

  The study presents valuable findings of an optimized E. coli cell-free protein synthesis (eCFPS) system that has been simplified by reducing the number of core components from 35 to 7; furthermore, the findings communicate a simplified 'fast lysate' preparation that eliminates the need for traditional runoff and dialysis steps. It is interesting that the system's robustness is exhibited by its applicability to nanoluc, a protein that expresses readily in many systems, to more challenging proteins like the functional self-assembling vimentin and the active restriction endonuclease Bsal. Despite the study representing an advancement towards simplifying protein expression workflows, the evidence supporting some of the claims remains incomplete: performance or efficiency claims of the new system needs to be supported by comparisons with typical cell free expression systems. Despite this shortcoming, the paper remains of interest to scientists in cell and molecular biology, microbiology, biotechnology and protein synthesis.

Reviewed by eLife

Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers

1. Xiaoyu Yu
2. Yuanjun He
3. Thedore M Kamenecka
4. Douglas J Kojetin

• Curated by eLife

  eLife Assessment

  This important study investigated whether the nuclear receptor Nur77 is regulated by a non-canonical mechanism of ligand-induced disruption of its interaction with RXRg, similar to the family member Nurr1. The overall evidence is compelling. This manuscript will be of interest to scientists focusing on mechanisms of transcriptional regulation.

Reviewed by eLife

Exogenous Amyloid Sequences: Their Role in Amyloid-Beta Heterotypic Aggregation

1. Jofre Seira Curto
2. Marina Romero Ruiz
3. Genís Pérez Collell
4. Sandra Villegas
5. Maria Rosario Fernandez
6. Natalia Sanchez de Groot

Reviewed by preLights

Distinct mechanisms of inhibition of Kv2 potassium channels by tetraethylammonium and RY785

1. Shan Zhang
2. Robyn Stix
3. Esam A Orabi
4. Nathan Bernhardt
5. José D Faraldo-Gómez

• Curated by eLife

  eLife Assessment

  This study represents an important advance in our understanding of how certain inhibitors affect the behavior of voltage gated potassium channels. Robust molecular dynamics simulation and analysis methods lead to a new proposed inhibition mechanism with convincing strength of support. This study has considerable significance for the fields of ion channel physiology and pharmacology and could aid in development of selective inhibitors for protein targets.

Reviewed by eLife

A potential anti-amyloidogenic therapy for type 2 diabetes based on the QBP1 peptide

1. María M. Tejero-Ojeda
2. Ada Bernaus Vives
3. Michal Wojciechowski
4. Dinh Quoc Huy Pham
5. Mateusz Chwastyk
6. Mario Vallejo
7. Anna Novials
8. Mariano Carrión-Vázquez

Reviewed by preLights

Membrane curvature regulates Ups1 dependent phosphatidic acid transfer across lipid bilayers

1. Fereshteh Sadeqi
2. Dexin Dong
3. Kai Stroh
4. Marian Vache
5. Jutta Metz
6. Dietmar Riedel
7. Andreas Janshoff
8. Herre Jelger Risselada
9. Caroline Kolenda
10. Michael Meinecke

• Curated by eLife

  eLife Assessment

  This fundamental study combines in vitro reconstitution experiments and molecular dynamics simulations to elucidate how membrane lipids are transported from the outer to the inner membrane of mitochondria. The authors provide convincing evidence that a positive membrane curvature is critical for membrane lipid extraction. The work will be of broad interest to cell biologists and biochemists.

Reviewed by eLife

An Automated End-to-End Workflow for Production of Secreted Proteins in Transfected Mammalian Cells

1. Pavee Vasnarungruengkul
2. Michael A. Anaya
3. Annie W. Lam
4. Elisa Gonzalez
5. An Zhang
6. Maxine L. Wang
7. Woj M. Wojtowicz
8. Kai Zinn
9. Jost Vielmetter

Reviewed by Arcadia Science

Kinesin-1 conformational dynamics are controlled by a cargo-sensitive TPR switch

1. Shivam Shukla
2. Jessica A Cross
3. Monika Kish
4. Sathish KN Yadav
5. Johannes F Weijman
6. Laura O'Regan
7. Judith Mantell
8. Ufuk Borucu
9. Xiyue Leng
10. Christiane Schaffitzel
11. Jonathan J Phillips
12. Derek N Woolfson
13. Mark P Dodding

• Curated by eLife

  eLife Assessment

  The revised manuscript by Shukla et al. provides important mechanistic insights into kinesin-1 autoinhibition and cargo-mediated activation. Through a convincing integration of protein engineering, computational modeling, biophysical assays, HDX-MS, and electron microscopy, the study delineates how cargo binding induces an allosteric transition that propagates along the coiled-coil stalk to the motor domains, enhancing MAP7 engagement. The revisions substantially improve clarity, figure annotation, and methodological transparency, leaving the remaining limitations, primarily those inherent to conformational heterogeneity and resolution, appropriately acknowledged. Overall, the updated manuscript presents a coherent mechanism for kinesin-1 activation that will be of broad interest to the motor protein, structural biology, and cell biology communities.

Reviewed by eLife

Elucidating the kinetic and thermodynamic insight into regulation of glycolysis by lactate dehydrogenase and its impact on tricarboxylic acid cycle and oxidative phosphorylation in cancer cells

1. Siying Zeng
2. Yuqi Wang
3. Minfeng Ying
4. Chengmeng Jin
5. Chang Ying
6. Di Wang
7. Hao Wu
8. Xun Hu

• Curated by eLife

  eLife Assessment

  This study presents an assessment of the effect of lactate dehydrogenase (LDH) inhibition on the activity of glycolysis and tricarboxylic acid cycle. The data were collected and analyzed using solid and validated methodology. This paper makes a useful contribution to the field as it considers a control analysis of LDH flux. The findings differ from other published findings likely due to the time course of the incubations used to assess metabolism. While such comparative studies were not presented in the manuscript, the manuscript should be interpreted in light of this critical distinction.

Reviewed by eLife