Biophysics

TMEM16 and OSCA/TMEM63 proteins share a conserved potential to permeate ions and phospholipids

1. Augustus J Lowry
2. Pengfei Liang
3. Mo Song
4. Yuichun Wan
5. Zhen-Ming Pei
6. Huanghe Yang
7. Yang Zhang

• Curated by eLife

  eLife Assessment

  This important study advances our understanding of the mechanisms controlling lipid flux and ion permeation in the TMEM16 and OSCA/TMEM63 family channels. The study provides compelling new evidence indicating that side chains along the TM4/6 interface play a key role in gating lipid and ion fluxes in these channels. The authors suggest that the transmembrane channel/scramblase family proteins may have originally functioned as scramblases but lost this capacity over evolution.

Reviewed by eLife

HIV integrase compacts viral DNA into biphasic condensates

1. Pauline J Kolbeck
2. Marjolein de Jager
3. Margherita Gallano
4. Tine Brouns
5. Ben Bekaert
6. Wout Frederickx
7. Sebastian F Konrad
8. Siska Van Belle
9. Frauke Christ
10. Steven De Feyter
11. Zeger Debyser
12. Laura Filion
13. Jan Lipfert
14. Willem Vanderlinden

• Curated by eLife

  eLife Assessment

  The manuscript by Kolbeck and co-workers is an important contribution to understanding the physical mechanism that controls a key step in the retroviral infectious cycle. The authors employ a wide range of experimental techniques, complemented with Montecarlo simulations, that result in convincing evidence of compaction of HIV DNA by the viral integrase. This manuscript would benefit from in-depth discussion and analysis of the biophysical implications of the results.

Reviewed by eLife

Protein-Induced Membrane Strain Drives Supercomplex Formation

1. Maximilian C Pöverlein
2. Alexander Jussupow
3. Hyunho Kim
4. Ville RI Kaila

• Curated by eLife

  eLife Assessment

  In this potentially important study, the authors conducted extensive atomistic and coarse-grained simulations as well as a lattice Monte Carlo analysis to probe the driving force and functional impact of supercomplex formation in the inner mitochondrial membrane. The study highlighted the importance of membrane mechanics to the supercomplex formation and revealed differences in structural and dynamical features of the protein components upon complex formation. In its current form, the analysis is considered incomplete, especially concerning the contributions of membrane mechanics and allosteric coupling of key regions.

Reviewed by eLife

Multi-pass, single-molecule nanopore reading of long protein strands with single-amino acid sensitivity

1. Keisuke Motone
2. Daphne Kontogiorgos-Heintz
3. Jasmine Wee
4. Kyoko Kurihara
5. Sangbeom Yang
6. Gwendolin Roote
7. Yishu Fang
8. Nicolas Cardozo
9. Jeff Nivala

Reviewed by preLights

Exploring breast cancer-related biochemical changes in circulating extracellular vesicles using Raman spectroscopy

1. Arianna Bonizzi
2. Lorena Signati
3. Maria Grimaldi
4. Marta Truffi
5. Francesca Piccotti
6. Stella Gagliardi
7. Giulia Dotti
8. Serena Mazzucchelli
9. Sara Albasini
10. Roberta Cazzola
11. Debanjan Bhowmik
12. Chandrabhas Narayana
13. Fabio Corsi
14. Carlo Morasso

Reviewed by Arcadia Science

Fluid mechanics of luminal transport in actively contracting endoplasmic reticulum

1. Pyae Hein Htet
2. Edward Avezov
3. Eric Lauga

• Curated by eLife

  eLife Assessment

  This work explores the physical principles underlying fluid flow and luminal transport within the endoplasmic reticulum. Its important contribution is to highlight the strong physical constraints imposed by viscous dissipation in nanoscopic tubular networks. In particular, the work presents convincing evidence based on theoretical analysis that commonly discussed mechanisms such as tubular contraction are unlikely to be at the origin of the observed transport velocities. As such, it will be of relevance to cell biologists and physicists interested in organelle dynamics. As this study is solely theoretical and deals with order of magnitude estimates, its main conclusions await experimental validation.

Reviewed by eLife

Conservation of the cooling agent binding pocket within the TRPM subfamily

1. Kate Huffer
2. Matthew CS Denley
3. Elisabeth V Oskoui
4. Kenton J Swartz

• Curated by eLife

  eLife Assessment

  In this valuable study, Huffer et al posit that non-cold sensing members of the TRPM subfamily of ion channels (e.g., TRPM2, TRPM4, TRPM5) contain a binding pocket for icilin that overlaps with the one found in the cold-activated TRPM8 channel. After examining a body of TRP channel cryo-EM structures to identify the conserved site, this study presents convincing electrophysiological evidence supporting the presence of an icilin binding pocket within TRPM4. This study shows that icilin has modulatory effects on the TRPM4 channel and will be of direct interest to those working in the TRP-channel field, but it also has implications for studies of somatosensation, taste, as well as pharmacological targeting of the TRPM subfamily.

Reviewed by eLife

Structure of scavenger receptor SCARF1 and its interaction with lipoproteins

1. Yuanyuan Wang
2. Fan Xu
3. Guangyi Li
4. Chen Cheng
5. Bowen Yu
6. Ze Zhang
7. Dandan Kong
8. Fabao Chen
9. Yali Liu
10. Zhen Fang
11. Longxing Cao
12. Yang Yu
13. Yijun Gu
14. Yongning He

• Curated by eLife

  eLife Assessment

  SCARF1 is a scavenger membrane-bound receptor that binds modified versions of lipoproteins and has a significant role in maintaining lipid homeostasis. This useful study reports the crystal structure of SCARF1 and identifies putative binding sites for modified lipoproteins. Supported by a convincing set of experimental approaches, this study advances our knowledge of how scavenger receptors clear modified lipoproteins to maintain lipid homeostasis.

Reviewed by eLife

TRPML1 gating modulation by allosteric mutations and lipids

1. Ninghai Gan
2. Yan Han
3. Weizhong Zeng
4. Youxing Jiang

• Curated by eLife

  eLife Assessment

  Transient receptor potential mucolipin 1 (TRPML1) functions as a lysosomal ion channel whose variants are associated with lysosomal storage disorder mucolipidosis type IV. This important report describes local and global structural changes driven by binding of regulatory phospholipids and by mutations that allosterically cause gain or loss of channel function. Most of the claims related to the allosteric regulation of TRPML1 are convincingly supported by two new cryo-EM structures which are evaluated within the context of previously reported TRPML1 structures, and a proposed allosteric gating mechanism is partially supported by functional electrophysiology results.

Reviewed by eLife

Water and chloride as allosteric inhibitors in WNK kinase osmosensing

1. Liliana R Teixeira
2. Radha Akella
3. John M Humphreys
4. Haixia He
5. Elizabeth J Goldsmith

• Curated by eLife

  eLife Assessment

  This study presents an important investigation of water coordination in a specific kinase family with a focus on the regulation of osmosensing protein kinases. X-ray crystallographic approaches combined with functional assays are used to address the hypothesis that bound water participates in the osmosensing mechanism as an allosteric kinase inhibitor. The evidence for changes in kinase conformation and space group of the crystal as a function of added low molecular weight polyethylene glycol is solid. The work will be of considerable interest to the kinase field as well as colleagues studying allosteric regulation of protein function.

Reviewed by eLife