Latest preprint reviews

1. 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

2. 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

3. 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

   Reviewed by Biophysics Colab

4. Structure of an open K _ATP channel reveals tandem PIP ₂ 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

5. 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

6. Structural insights into the organization and channel properties of human Pannexin isoforms 1 and 3

   This article has 8 authors:

   1. Nazia Hussain
   2. Ashish Apotikar
   3. Shabareesh Pidathala
   4. Sourajit Mukherjee
   5. Ananth Prasad Burada
   6. Sujit Kumar Sikdar
   7. Vinothkumar R. Kutti
   8. Aravind Penmatsa

   Reviewed by Biophysics Colab

7. Dynamic allosteric networks drive adenosine A1 receptor activation and G-protein coupling

   This article has 2 authors:

   1. Miguel A Maria-Solano
   2. Sun Choi

   This article has been curated by 2 groups:

   • Curated by eLife

     eLife assessment

     The authors describe the dynamics underlying allostery of the adenosine A1 receptor, providing valuable insights into the receptor's activation pathway. The enhanced sampling molecular dynamics simulations of available structural data, followed by network analysis, reveal transient conformational states and communication between functional regions. The authors carefully state the limitations of their work, including the restricted convergence of the free energy landscape and missing water-mediated hydrogen bond coordination. Collectively, they provide a convincing framework for advancing rational design strategies of specific modulators with desired modes of action.

     [Editors' note: this was originally reviewed and assessed by Biophysics Colab]

   • Curated by Biophysics Colab

     Evaluation statement (16 June 2023)

     Maria-Solano and Choi present the dynamics underlying allostery of the adenosine A1 receptor, providing valuable insights into the receptor's activation pathway. The enhanced sampling molecular dynamics simulations of available structural data, followed by network analysis, reveal transient conformational states and communication between functional regions. The authors carefully state the limitations of their work, including the restricted convergence of the free energy landscape and missing water-mediated hydrogen bond coordination. Collectively, the findings provide a convincing framework to advance rational design strategies of specific modulators with desired modes of action.

     Biophysics Colab considers this to be a convincing study and recommends it to scientists interested in the structural dynamics, allosteric pathway activations, and free energy landscapes of GPCRs.

     (This evaluation by Biophysics Colab refers to version 5 of this preprint, which has been revised in response to peer review of versions 3 and 4.)

   Reviewed by eLife, Biophysics Colab

8. Intracellular helix-loop-helix domain modulates inactivation kinetics of mammalian TRPV5 and TRPV6 channels

   This article has 4 authors:

   1. Lisandra Flores-Aldama
   2. Daniel Bustos
   3. Deny Cabezas-Bratesco
   4. Sebastián E. Brauchi

   This article has been curated by 1 group:

   • Curated by Biophysics Colab

     Evaluation statement (1 September 2023)

     Flores-Aldama and colleagues set out to identify molecular determinants of fast inactivation in the TRPV6 ion channel, a mechanism not observed in the closely related TRPV5 channel. The work focuses on a helix-loop-helix (HLH) motif, located at the interface between several important regions for channel gating. Using molecular dynamics simulations and analysis of mutations, the authors identify pairs of amino acid residues in a structural triad formed by the HLH, S2-S3 linker, and transmembrane domains, which show different conformations in the available TRPV5 and TRPV6 cryo-EM structures. An important aspect of the study is that some of the structural hypotheses were derived from an evolutionary analysis of sequences from orthologues of both channels, demonstrating the value of this type of analysis.

     Biophysics Colab considers this to be a convincing study and recommends it to scientists interested in the molecular determinants of ion channel gating.

     (This evaluation by Biophysics Colab 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. Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants

   This article has 4 authors:

   1. Dongxue Yang
   2. Zhiyu Zhao
   3. Emad Tajkhorshid
   4. Eric Gouaux

   This article has been curated by 1 group:

   • Curated by Biophysics Colab

     Evaluation statement (24 May 2023)

     Yang et al. present valuable information about ligand interactions with the serotonin transporter SERT, innovatively purified from pig brain using Fab fragments. The approach of using natively expressed SERT is notable for its potential insight into binding of endogenous membrane components such as lipids. Data distinguishing binding of the psychostimulants methamphetamine and cocaine add to our knowledge of substrate and inhibitor interactions with SERT and allow direct comparison with the closely related dopamine transporter DAT. The authors carefully state the limitations of their findings, including the possibility that the monomeric transporter stable in detergent micelles might exist in a multimeric state in native membranes.

     Biophysics Colab considers this to be a convincing study and recommends it to scientists interested in the structure, mechanism and ligand interactions of neurotransmitter transporters.

     (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. Tuning aromatic contributions by site-specific encoding of fluorinated phenylalanine residues in bacterial and mammalian cells

    This article has 12 authors:

    1. Grace D. Galles
    2. Daniel T. Infield
    3. Colin J. Clark
    4. Marcus L. Hemshorn
    5. Shivani Manikandan
    6. Frederico Fazan
    7. Ali Rasouli
    8. Emad Tajkhorshid
    9. Jason D. Galpin
    10. Richard B. Cooley
    11. Ryan A. Mehl
    12. Christopher A. Ahern

    This article has been curated by 1 group:

    • Curated by Biophysics Colab

      Endorsement statement (3 October 2022)

      The preprint by Galles et al. reports the generation of pyrrolysine-based aminoacyl-tRNA synthetases capable of incorporating fluorinated phenylalanine non-canonical amino acids into proteins expressed in either bacteria or mammalian cells. For the most extensively characterized synthetases, fluorinated phenylalanine derivatives were successfully incorporated into GFP and two membrane proteins (CFTR and Nav1.5) at expression levels adequate for biochemical studies, suggesting that the approach could be combined with multiple different structural and biophysical techniques. The work provides a valuable tool that will enable the functional role of cation-pi interactions to be interrogated in both soluble and integral membrane proteins.

      (This endorsement 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