The structure of HiSiaQM defines the architecture of tripartite ATP-independent periplasmic (TRAP) transporters

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

• 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

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

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

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

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

Structural basis of ion – substrate coupling in the Na ⁺ -dependent dicarboxylate transporter VcINDY

1. David B. Sauer
2. Jennifer J. Marden
3. Joseph C. Sudar
4. Jinmei Song
5. Christopher Mulligan
6. Da-Neng Wang

• 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

Chloride ions evoke taste sensations by binding to the extracellular ligand-binding domain of sweet/umami taste receptors

1. Nanako Atsumi
2. Keiko Yasumatsu
3. Yuriko Takashina
4. Chiaki Ito
5. Norihisa Yasui
6. Robert F. Margolskee
7. Atsuko Yamashita

• 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 Biophysics Colab, eLife

The dopamine transporter counter-transports potassium to increase the uptake of dopamine

1. Claus Loland
2. Solveig Schmidt
3. Mette Malle
4. Anne Nielsen
5. Søren Bohr
6. Ciara Pugh
7. Jeppe Nielsen
8. Ida Poulsen
9. Kasper Rand
10. Nikos Hatzakis

Reviewed by Biophysics Colab

TMEM16 scramblases thin the membrane to enable lipid scrambling

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

• 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

The versatile regulation of K _2P channels by polyanionic lipids of the phosphoinositide (PIP ₂ ) and fatty acid metabolism (LC-CoA)

1. Elena B. Riel
2. Björn C. Jürs
3. Sönke Cordeiro
4. Marianne Musinszki
5. Marcus Schewe
6. Thomas Baukrowitz

Reviewed by Biophysics Colab

Fast ATP-dependent Subunit Rotation in Reconstituted F _o F ₁ -ATP Synthase Trapped in Solution

1. Thomas Heitkamp
2. Michael Börsch

• 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

Mechanism of CFTR correction by type I folding correctors

1. Karol Fiedorczuk
2. Jue Chen

• 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