Latest preprint reviews

1. Interpreting the molecular mechanisms of disease variants in human transmembrane proteins

   This article has 4 authors:

   1. Johanna Katarina Sofie Tiemann
   2. Henrike Zschach
   3. Kresten Lindorff-Larsen
   4. Amelie Stein

   Reviewed by Biophysics Colab

2. 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. Maru Orozco-Contreras
   3. Gisela E Rangel-Yescas
   4. Leon 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

3. Integrated AlphaFold2 and DEER investigation of the conformational dynamics of a pH-dependent APC antiporter

   This article has 6 authors:

   1. Diego del Alamo
   2. Lillian DeSousa
   3. Rahul M. Nair
   4. Suhaila Rahman
   5. Jens Meiler
   6. Hassane S. Mchaourab

   Reviewed by Biophysics Colab

4. 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

5. 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

6. Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter

   This article has 17 authors:

   1. Martin F. Peter
   2. Jan A. Ruland
   3. Peer Depping
   4. Niels Schneberger
   5. Emmanuele Severi
   6. Jonas Moecking
   7. Karl Gatterdam
   8. Sarah Tindall
   9. Alexandre Durand
   10. Veronika Heinz
   11. Jan Peter Siebrasse
   12. Paul-Albert Koenig
   13. Matthias Geyer
   14. Christine Ziegler
   15. Ulrich Kubitscheck
   16. Gavin H. Thomas
   17. 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

7. Calcineurin-fusion facilitates Cryo-EM Structure Determination of a Family A GPCR

   This article has 8 authors:

   1. Jun Xu
   2. Geng Chen
   3. Haoqing Wang
   4. Sheng Cao
   5. Jie Heng
   6. Xavier Deupi
   7. Yang Du
   8. Brian K. Kobilka

   Reviewed by Biophysics Colab

8. Combinatorial G x G x E CRISPR screening and functional analysis highlights SLC25A39 in mitochondrial GSH transport

   This article has 11 authors:

   1. Xiaojian Shi
   2. Bryn Reinstadler
   3. Hardik Shah
   4. Tsz-Leung To
   5. Katie Byrne
   6. Luanna Summer
   7. Sarah E. Calvo
   8. Olga Goldberger
   9. John G. Doench
   10. Vamsi K. Mootha
   11. Hongying Shen

   Reviewed by Biophysics Colab

9. 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

10. 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