Biophysics

Structural mechanisms of PIP2 activation and SEA0400 inhibition in human cardiac sodium-calcium exchanger NCX1

1. Jing Xue
2. Weizhong Zeng
3. Scott John
4. Nicole Attiq
5. Michela Ottolia
6. Youxing Jiang

• Curated by eLife

  eLife Assessment

  Cardiac Ca2+/Na+ exchange is mediated by the NCX1 antiporter, whose activity is tightly regulated. This important manuscript describes the structural basis of activation by the lipid DiC8-PIP2 and inhibition by binding of a small molecule to NCX1. These results provide convincing insights into NCX1 regulation and the structural basis of cellular Ca2+ signaling.

Reviewed by eLife

Protein Language Model Identifies Disordered, Conserved Motifs Driving Phase Separation

1. Yumeng Zhang
2. Jared Zheng
3. Bin Zhang

• Curated by eLife

  eLife Assessment

  This valuable study presents an analysis of evolutionary conservation in intrinsically disordered regions, identified as key drivers of phase separation, leveraging a protein language model. The strength of evidence is potentially compelling, but a clearer justification of the methods and analyses is needed to fully support the main claims.

Reviewed by eLife

Structural and dynamic impacts of single-atom disruptions to guide RNA interactions within the recognition lobe of Geobacillus stearothermophilus Cas9

1. Helen B Belato
2. Alexa L Knight
3. Alexandra M D'Ordine
4. Chinmai Pindi
5. Zhiqiang Fan
6. Jinping Luo
7. Giulia Palermo
8. Gerwald Jogl
9. George P Lisi

• Curated by eLife

  eLife Assessment

  This study offers valuable insights into the conformational dynamics of the nucleic acid recognition lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. The authors investigate the influence of local dynamics and allosteric regulation on guide RNA binding affinity and DNA cleavage specificity through molecular dynamics simulations, advanced NMR techniques, RNA binding studies, and mutagenesis. While the mutations studied do not lead to significant changes in GeoCas9 cleavage activity, the study provides convincing evidence for the role of allosteric mechanisms and interdomain communication in Cas9 enzymes, and will be of great interest to biochemists and biophysicists exploring these complex systems.

Reviewed by eLife

Raman flow cytometry using time-delay integration

1. Matthew Lindley
2. Toshiki Kubo
3. Stéphanie Devineau
4. Menglu Li
5. Jing Qiao
6. Takuya Yashiro
7. Shiroh Iwanaga
8. Kazuyo Moro
9. Katsumasa Fujita

Reviewed by Arcadia Science

Responses to membrane potential-modulating ionic solutions measured by magnetic resonance imaging of cultured cells and in vivo rat cortex

1. Kyeongseon Min
2. Sungkwon Chung
3. Seung-Kyun Lee
4. Jongho Lee
5. Phan Tan Toi
6. Daehong Kim
7. Jung Seung Lee
8. Jang-Yeon Park

• Curated by eLife

  eLife Assessment

  The authors show MRI relaxation time changes that are claimed to originate from cell membrane potential changes. This would be a substantial contribution if true because it may provide a mechanism whereby membrane potential changes could be inferred noninvasively. However, the membrane potential manipulations applied here are performed on a slow time scale and are known to induce cell swelling. Cell swelling has been previously shown to affect relaxation time. Experiments could be performed to rule out this hypothesis, but the authors have chosen not to perform these experiments. The study is therefore useful, but the evidence is incomplete.

Reviewed by eLife

Scaling and merging macromolecular diffuse scattering with mdx2

1. Steve P. Meisburgera
2. Nozomi Andob

Reviewed by Arcadia Science

ATP-release pannexin channels are gated by lysophospholipids

1. Erik Henze
2. Russell N Burkhardt
3. Bennett William Fox
4. Tyler J Schwertfeger
5. Eric Gelsleichter
6. Kevin Michalski
7. Lydia Kramer
8. Margret Lenfest
9. Jordyn M Boesch
10. Hening Lin
11. Frank C Schroeder
12. Toshimitsu Kawate

• Curated by eLife

  eLife Assessment

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The study by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide compelling evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels. The work will be of interest to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  [Editors' note: this paper was reviewed and curated by Biophysics Colab]

• Curated by Biophysics Colab

  Evaluation Statement (5 February 2025)

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The preprint by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels.

  Biophysics Colab recommends this study to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  Biophysics Colab has evaluated this study as one that meets the following criteria:

  • Rigorous methodology
  • Transparent reporting
  • Appropriate interpretation

  (This evaluation refers to version 3 of this preprint, which has been revised in response to peer review of versions 1 and 2.)

Reviewed by eLife, Biophysics Colab

A mathematical model clarifies the ABC Score formula used in enhancer-gene prediction

1. Joseph Nasser
2. Kee-Myoung Nam
3. Jeremy Gunawardena

• Curated by eLife

  eLife Assessment

  This important study dissects the mathematical and biological assumptions underlying the commonly used Activity-by-Contact model of enhancer action in transcriptional regulation. The authors provide a convincing mathematical analysis that links this (mostly phenomenological) model to concrete molecular mechanisms of enhancer function. This work provides a strong foundation from which to analyze a broad swath of genome-wide data such as that generated by CRISPRi screens.

Reviewed by eLife

Geometry effects on protein mobility in a synapse

1. Simon Dannenberg
2. Sofiia Reshetniak
3. Sarah Mohammadinejad
4. Silvio O. Rizzoli
5. Stefan Klumpp

Reviewed by PREreview

Arp2/3-mediated bidirectional actin assembly by SPIN90 dimers in metazoans

1. Tianyang Liu
2. Luyan Cao
3. Miroslav Mladenov
4. Guillaume Romet-Lemonne
5. Michael Way
6. Carolyn A. Moores

Reviewed by Arcadia Science