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  1. 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

    This article has 3 evaluationsAppears in 3 listsLatest version Latest activity
  2. Activation mechanism of the human Smoothened receptor

    This article has 3 authors:
    1. Prateek D. Bansal
    2. Soumajit Dutta
    3. Diwakar Shukla
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Evaluation statement (22 August 2023)

      Bansal et al. present an atomistic view of the transition cascade of the class F GPCR Smoothened (Smo). The extensive long-range molecular dynamics simulations together with stochastic modelling provide theoretical insight into Smo activation and how this is modulated by different ligands. The work identifies testable hypotheses for functional studies of Smo and other class F GPCRs. Future simulations of regions beyond the seven-transmembrane bundle, particularly the cysteine-rich domain, will afford a more complete understanding of receptor activation.

      Biophysics Colab considers this to be a convincing computational study and recommends it to scientists interested in the conformational dynamics of class F GPCRs.

      (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

    This article has 3 evaluationsAppears in 3 listsLatest version Latest activity
  3. 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

    This article has 3 evaluationsAppears in 3 listsLatest version Latest activity
  4. Dynamic allosteric networks drive adenosine A 1 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

    This article has 5 evaluationsAppears in 7 listsLatest version Latest activity
  5. Activation-pathway transitions in human voltage-gated proton channels revealed by a non-canonical fluorescent amino acid

    This article has 4 authors:
    1. Esteban Suárez-Delgado
    2. M. E. Orozco-Contreras
    3. Gisela E. Rangel-Yescas
    4. LeĂłn D. Islas
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (22 December 2022)

      The preprint by Suarez-Delgado et al. explores the mechanisms by which the Hv1 voltage-activated proton channel is dependent upon transmembrane voltage and pH by incorporating the small fluorescent non-canonical amino acid Anap into the S4 helix and monitoring its fluorescence. Anap spectra suggest the fluorophore resides in an aqueous environment and moves relative to a quenching aromatic residue (F150) in the S2 helix upon depolarization. Two kinetically distinct components of fluorescence change support the presence of at least three conformational states in the activation pathway of Hv1. Measurements using different pH gradients suggest that S4 movement and channel opening are similarly affected by pH gradients. This is the first study to incorporate Anap into Hv1, and provide a rigorous and thorough characterization of how the fluorophore can be used to explore mechanisms of gating and regulation, paving the way for future studies. The work will be of interest to physiologists and biophysicists investigating membrane protein mechanisms using non-canonical fluorescent amino acids.

      (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

    This article has 3 evaluationsAppears in 3 listsLatest version Latest activity
  6. Membrane curvature governs the distribution of Piezo1 in live cells

    This article has 12 authors:
    1. Shilong Yang
    2. Xinwen Miao
    3. Steven Arnold
    4. Boxuan Li
    5. Alan T. Ly
    6. Huan Wang
    7. Matthew Wang
    8. Xiangfu Guo
    9. Medha M. Pathak
    10. Wenting Zhao
    11. Charles D. Cox
    12. Zheng Shi
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (6 December 2022)

      The preprint by Yang et al. asks how the shape of the membrane influences the localization of mechanosensitive Piezo channels. The authors use a creative approach involving methods that distort the plasma membrane by generating blebs and artificial filopodia. They convincingly show that curvature of the lipid environment influences Piezo1 localization, such that increased curvature causes channel depletion, and that application of the chemical modulator Yoda1 is sufficient to allow channels to enter filopodia. The study provides support for a provocative “flattening model” of Yoda1 action, and should inspire future studies by researchers interested in mechanosensitive channels and membrane curvature.

      (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

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  7. Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors

    This article has 7 authors:
    1. Nanako Atsumi
    2. Keiko Yasumatsu
    3. Yuriko Takashina
    4. Chiaki Ito
    5. Norihisa Yasui
    6. Robert F. Margolskee
    7. Atsuko Yamashita
    This article has been curated by 2 groups:
    • Curated by eLife

      eLife assessment

      This fundamental study presents solid evidence for T1r (sweet /umami) taste receptors as chloride (Cl-) receptors, based on a combination of state-of-the-art techniques to demonstrate that T1r receptors from Medaka fish bind chloride and that this binding induces a conformational change in the heteromeric receptor. This conformational change leads to low-concentration chloride-specific action potential firing in nerves from neurons containing these receptors in mice, results that represent an important advance in our understanding of the logic of taste perception.

    • Curated by Biophysics Colab

      Endorsement statement (17 November 2022)

      The preprint by Atsumi et al. describes how chloride binding to sweet- and umami-sensing proteins (T1R taste receptors) can evoke taste sensation. The authors use an elegant combination of structural, biophysical and electrophysiological approaches to locate a chloride binding site in the ligand-binding domain of medaka fish T1r2a/3 receptors. They convincingly show that low mM concentrations of chloride induce conformational changes and, using single fiber recordings, establish that mouse chorda tympani nerves are activated by chloride in a T1R-dependent manner. This suggests that chloride binding to sweet receptors could mediate the commonly reported sweet taste sensation following ingestion of low concentrations of table salt. The findings will be of broad relevance to those studying taste sensation and ligand recognition in GPCRs.

      (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 eLife, Biophysics Colab

    This article has 5 evaluationsAppears in 5 listsLatest version Latest activity
  8. 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

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  9. The structure of HiSiaQM defines the architecture of tripartite ATP-independent periplasmic (TRAP) transporters

    This article has 13 authors:
    1. Martin F. Peter
    2. Peer Depping
    3. Niels Schneberger
    4. Emmanuele Severi
    5. Karl Gatterdam
    6. Sarah Tindall
    7. Alexandre Durand
    8. Veronika Heinz
    9. Paul-Albert Koenig
    10. Matthias Geyer
    11. Christine Ziegler
    12. Gavin H. Thomas
    13. Gregor Hagelueken
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (5 August 2022)

      Peter et al. describe the first experimentally validated structural model of a canonical member of the TRAP family of transporters, Haemophilus influenzae (Hi)SiaPQM, which transports sialic acid into bacteria. By elegantly combining a cryo-EM structure of the HiSiaQM dimer, AlphaFoldmodels, and sequence, biochemical, and mutational analyses, the authors shed light on the fold and domain organization of the tripartite HiSiaPQM holocomplex. The authors also propose a structure-based model for its transport mechanism: substrate recognition is "outsourced" to the substrate binding protein (P protein) by the QM proteins, which in turn use an elevator mechanism to transport sialic acid across the membrane. The work is rigorous and convincing, and it presents valuable findings that will be of interest to scientists investigating transporters with an elevator-type mechanism as well as membrane transport more generally.

      (This endorsement 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

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  10. Structural basis of ion – substrate coupling in the Na + -dependent dicarboxylate transporter VcINDY

    This article has 6 authors:
    1. David B. Sauer
    2. Jennifer J. Marden
    3. Joseph C. Sudar
    4. Jinmei Song
    5. Christopher Mulligan
    6. Da-Neng Wang
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (28 June 2022)

      Sauer et al. describe two cryo-EM structures of the Na+-dependent dicarboxylate transporter VcINDY in two inward-facing states. The high-quality structural data, complemented by NMR-inspired analysis, functional assays and cysteine accessibility measurements, reveal crucial conformational changes induced by Na+ binding to apo VcINDY that result in formation of the substrate-binding site. This is a strong manuscript that provides an important contribution to our understanding of the transport mechanism in the SLC13/DASS family of transporters, several members of which have critical physiological functions. The work will be of interest to researchers working on this and other ion-coupled transporter families.

      (This endorsement 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

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  11. TMEM16 scramblases thin the membrane to enable lipid scrambling

    This article has 9 authors:
    1. Alessio Accardi
    2. Maria Falzone
    3. Zhang Feng
    4. Omar Alvarenga
    5. Yangang Pang
    6. Byoung Lee
    7. Xiaolu Cheng
    8. Eva Fortea
    9. Simon Scheuring
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Biophysics Colab

      Endorsement statement (11 May 2022)

      Falzone et al. report important new cryo-EM structures of the fungal calcium-activated lipid scramblase afTMEM16, as well as the functional impact of mutations and different lipid membrane compositions on lipid scrambling. Individual lipids are beautifully resolved around the subunit cavity involved in lipid scrambling in one of the highest resolution structures of a TMEM16 protein solved to date, enabling the role of these lipid-interacting residues to be interrogated. Collectively, the results suggest that afTMEM16 catalyzes lipid scrambling by thinning the membrane rather than providing a hydrophilic permeation pathway for lipids. The work represents an important contribution that will be of interest to scientists investigating the mechanisms of lipid scrambling and how membrane proteins interact with their lipid environment.

      (This endorsement 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

    This article has 3 evaluationsAppears in 2 listsLatest activity
  12. Mechanism of CFTR correction by type I folding correctors

    This article has 2 authors:
    1. Karol Fiedorczuk
    2. Jue Chen
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (27 April 2022)

      The preprint by Fiedorczuk and Chen presents structures of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in complex with type I correctors, a class of drug currently used to treat cystic fibrosis by targeting CFTR folding and stability. The strength of the paper lies in the consistency of the structural data with maturation and binding assays, as well as with much of the existing literature. Overall, the work represents a rigorous investigation of the mechanism of these drugs, and will be of interest to those who study cystic fibrosis, protein folding, and drug design.

      (This endorsement refers to version 1 of this preprint, which was peer reviewed by Biophysics Colab.)

    Reviewed by Biophysics Colab

    This article has 2 evaluationsAppears in 2 listsLatest version Latest activity
  13. Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel

    This article has 6 authors:
    1. Vishal R. Patel
    2. Arturo M. Salinas
    3. Darong Qi
    4. Shipra Gupta
    5. David J. Sidote
    6. Marcel P. Goldschen-Ohm
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (30 August 2021)

      The preprint by Patel et al. describes the development of a single molecule approach for studying individual ligand binding events in membrane proteins within native lipid environments. The approach represents an elegant way to investigate the dynamics of ligand binding, and potential relationships with conformational changes, in molecules embedded within physiological membranes. The work makes an important contribution that will be of interest to scientists working on molecular mechanisms in ion channels and other 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

    This article has 3 evaluationsAppears in 4 listsLatest version Latest activity
  14. Fast ATP-dependent Subunit Rotation in Reconstituted F o F 1 -ATP Synthase Trapped in Solution

    This article has 2 authors:
    1. Thomas Heitkamp
    2. Michael Börsch
    This article has been curated by 1 group:
    • Curated by Biophysics Colab

      Endorsement statement (21 September 2021)

      The preprint by Heitkamp and Börsch describes visualization of the fast ATP-dependent subunit rotation in reconstituted FoF1-ATP synthase using single-molecule FRET techniques. Using a highly innovative method for trapping single molecules, the authors were able to see the static and dynamic disorder of enzymes in solution, not possible in previous studies. The work makes important contributions to both understanding the structural dynamics of FoF1-ATP synthase and the development of methodologies to study single-molecule dynamics of other proteins in solution.

      (This endorsement refers to version 5 of this preprint, which was peer reviewed by Biophysics Colab.)

    Reviewed by Biophysics Colab

    This article has 2 evaluationsAppears in 3 listsLatest version Latest activity