Biophysics Colab

Latest preprint reviews

1. ATP-release pannexin channels are gated by lysophospholipids

   This article has 12 authors:

   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

   This article has been curated by 2 groups:

   • 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 (30 January 2025)

     Kay and Aminzare discuss a claim made in a prior publication that macromolecular condensation acts as a water buffering mechanism in cells to compensate for the effects of osmotic shock. The authors argue that, although such a buffer could temporarily maintain a transmembrane osmolality differential, this differential would drive water across the membrane to reach a steady-state in which osmolality within the cell equals osmolality outside the cell. Using the well-established pump-leak model for osmotic water transport, they further show that the timescale at which a water buffer could maintain a modest 10% osmolality differential across the membrane is at most one minute for a typical animal cell.

     Biophysics Colab recommends this study to researchers working on membrane transport, intracellular water buffering, and condensate biology.

     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

2. Structure and function of the human mitochondrial MRS2 channel

   This article has 7 authors:

   1. Zhihui He
   2. Yung-Chi Tu
   3. Chen-Wei Tsai
   4. Jonathan Mount
   5. Jingying Zhang
   6. Ming-Feng Tsai
   7. Peng Yuan

   This article has been curated by 1 group:

   • Curated by Biophysics Colab

     Evaluation Statement (14 June 2024)

     The study by He et al. explores the structure and mechanisms of the human mitochondrial RNA splicing 2 (MRS2) protein, predicted to form Mg2+-selective channels in the mitochondrial inner membrane based on homology to the CorA family of prokaryotic Mg2+ channels. The authors use an innovative biochemical strategy to express MRS2 and perform single particle reconstructions in the absence and presence of key divalent cations. High resolution reconstructions of the pentameric channel reveal binding sites for Mg2+ and Ca2+, and electrophysiological investigations suggest that MRS2 is a Ca2+-regulated, cation-selective, Mg2+-permeable channel, in contrast to the Mg2+-regulated, Mg2+-selective CorA channel. This is an important study with interesting structural and functional observations, which will motivate further investigations of a potential role for MRS2 in mitochondrial Ca2+ signaling.

     Biophysics Colab recommends this study to scientists interested in the structure, function and regulation of cation channels as well as those working on mitochondrial transport.

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

     - Rigorous methodology

     - Transparent reporting

     - Appropriate interpretation

     (This evaluation refers to the version of record for this work, which is linked to and has been revised from the original preprint following peer review.)

   Reviewed by Biophysics Colab

3. ATP-release pannexin channels are gated by lysophospholipids

   This article has 12 authors:

   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

   This article has been curated by 2 groups:

   • 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 (30 January 2025)

     Kay and Aminzare discuss a claim made in a prior publication that macromolecular condensation acts as a water buffering mechanism in cells to compensate for the effects of osmotic shock. The authors argue that, although such a buffer could temporarily maintain a transmembrane osmolality differential, this differential would drive water across the membrane to reach a steady-state in which osmolality within the cell equals osmolality outside the cell. Using the well-established pump-leak model for osmotic water transport, they further show that the timescale at which a water buffer could maintain a modest 10% osmolality differential across the membrane is at most one minute for a typical animal cell.

     Biophysics Colab recommends this study to researchers working on membrane transport, intracellular water buffering, and condensate biology.

     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

4. AlphaFold-SFA: accelerated sampling of cryptic pocket opening, protein-ligand binding and allostery by AlphaFold, slow feature analysis and metadynamics

   This article has 4 authors:

   1. Shray Vats
   2. Raitis Bobrovs
   3. Pär Söderhjelm
   4. Soumendranath Bhakat

   Reviewed by Biophysics Colab

5. The folding-limited nucleation of curli hints at an evolved safety mechanism for functional amyloid production

   This article has 6 authors:

   1. Jolyon K. Claridge
   2. Chloe Martens
   3. Brajabandhu Pradhan
   4. Frank Sobott
   5. Mike Sleutel
   6. Han Remaut

   Reviewed by Biophysics Colab

6. Structural basis of closed groove scrambling by a TMEM16 protein

   This article has 3 authors:

   1. Zhang Feng
   2. Omar E. Alvarenga
   3. Alessio Accardi

   This article has been curated by 1 group:

   • Curated by Biophysics Colab

     Evaluation statement (17 January 2024; revised 31 January 2024)

     Feng and colleagues investigate the molecular basis of lipid scrambling in a fungal member of the TMEM16 family of Ca²⁺-dependent lipid scramblases. These proteins possess a groove in their 3D structure that has been implicated in lipid scrambling, which the authors investigate in the absence and presence of Ca²⁺ using a combination of cryo-EM structure determination, mutagenesis and functional assays. Their closed-groove structure reveals a continuous file of lipid molecules around the catalytic groove region, providing a structural basis for lipid interaction with the protein. Additionally, the authors capture three novel states of TMEM16, completing the picture of conformational transitions that this protein undergoes. Strikingly, the authors show that both structure and distribution of the protein’s conformations depend on lipid composition and nanodisc scaffold protein.

     Biophysics Colab considers this to be exceptional work and recommends it to scientists interested in plasma membrane lipid homeostasis and cryoEM.

     (This evaluation by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

   Reviewed by Biophysics Colab

7. Semi‐synthetic nanobody‐ligand conjugates exhibit tunable signaling properties and enhanced transcriptional outputs at neurokinin receptor‐1

   This article has 2 authors:

   1. Nayara Braga Emidio
   2. Ross W. Cheloha

   Reviewed by Biophysics Colab

8. Ion channel thermodynamics studied with temperature jumps measured at the cell membrane

   This article has 4 authors:

   1. Carlos A.Z. Bassetto
   2. Bernardo I. Pinto
   3. Ramon Latorre
   4. Francisco Bezanilla

   This article has been curated by 1 group:

   • Curated by Biophysics Colab

     Evaluation statement (17 January 2024)

     The study by Bassetto Jr. et al. presents an elegant and pioneering technique to rapidly manipulate membrane temperature by up to 10 ºC in less than 1.5 ms, thereby enabling high temporal resolution of the temperature dependence of ion channel currents. The approach combines the cut-open oocyte voltage clamp technique with laser illumination to heat the sub-membrane melanosome layer. Temperature is quantified from observed changes in membrane capacitance. Recordings of Kir1.1, TRPM8, and TRPV1 channels are used to validate the effectiveness of the technique. A limitation is that, in its current form, the technique can be used only on melanosome-containing Xenopus oocyte membranes.

     Biophysics Colab recommends this study to scientists working on the temperature dependence of ion channels and other membrane proteins.

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

     • Rigorous methodology
     • Transparent reporting
     • Appropriate interpretation

     (This evaluation refers to the version of record for this work, which is linked to and has been revised from the original preprint following peer review.)

   Reviewed by Biophysics Colab

9. Structure of an open KATP channel reveals tandem PIP2 binding sites mediating the Kir6.2 and SUR1 regulatory interface

   This article has 5 authors:

   1. Camden M. Driggers
   2. Yi-Ying Kuo
   3. Phillip Zhu
   4. Assmaa ElSheikh
   5. Show-Ling Shyng

   This article has been curated by 1 group:

   • Curated by Biophysics Colab

     Evaluation statement (10 January 2024)

     Driggers et al. is an elegant study that reports the structure of an open KATP channel complex formed from the Q52R diabetes mutation of the pore-forming subunit Kir 6.2, the sulfonylurea receptor (SUR1), and long-chain phosphatidylinositol 4,5-bisphosphate (PIP2) – a key lipid that stabilizes the open state of the channel and regulates inhibition by intracellular ATP. The structure reveals one PIP2 site related to that seen in other Kir channels as well as a second unanticipated one where the lipid snuggles into the interface between Kir6.2 and a region of SUR1 previously implicated in promoting the open state of KATP. This important finding helps to explain how PIP2 exerts such a profound regulatory influence on KATP.

     Biophysics Colab considers this to be a convincing study and recommends it to scientists working on KATP and other membrane proteins regulated by PIP2.

     (This evaluation by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

   Reviewed by Biophysics Colab

10. Constitutive activity of ionotropic glutamate receptors via hydrophobic substitutions in the ligand-binding domain

    This article has 5 authors:

    1. Sandra Seljeset
    2. Oksana Sintsova
    3. Yuhong Wang
    4. Hassan Y. Harb
    5. Timothy Lynagh

    This article has been curated by 1 group:

    • Curated by Biophysics Colab

      Evaluation statement (8 March 2024)

      Seljeset et al. investigate the mechanism by which NMDA receptors are activated by co-agonists glutamate and glycine. By mutating residue Asp732 in the glycine-binding site, they generate receptors activated by glutamate, and not glycine, but inhibited by glycine antagonists. Conventional and unnatural amino acid mutagenesis reveals that Asp732 interacts with nearby residues to influence channel gating as well as ligand binding. Furthermore, a homomeric receptor from Trichoplax adhaerens, which has a tyrosine in the homologous position, displays constitutive activity that becomes glycine-dependent when the tyrosine is mutated to aspartate. The study is valuable because it reveals the importance of position 732 for controlling ligand potency and channel activity in glutamate receptors, which should lead to a better understanding of how these receptors are primed for channel opening.

      Biophysics Colab recommends this study to scientists interested in the structure and function of glutamate receptors

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

      • Rigorous methodology
      • Transparent reporting
      • Appropriate interpretation

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

    Reviewed by Biophysics Colab