Biophysics

Ultrastructural insights into the microsporidian infection apparatus reveal the kinetics and morphological transitions of polar tube and cargo during host cell invasion

1. Himanshu Sharma
2. Nathan Jespersen
3. Kai Ehrenbolger
4. Lars-Anders Carlson
5. Jonas Barandun

Reviewed by Review Commons

Ligand bias underlies differential signaling of multiple FGFs via FGFR1

1. Kelly Karl
2. Nuala Del Piccolo
3. Taylor Light
4. Tanaya Roy
5. Pooja Dudeja
6. Vlad-Constantin Ursachi
7. Bohumil Fafilek
8. Pavel Krejci
9. Kalina Hristova

• Curated by eLife

  eLife assessment

  This manuscript describes useful data on the mechanisms underlying the activation of the receptor tyrosine kinase FGFR1 and stimulation of intracellular signaling pathways in response to FGF4, FGF8, or FGF9 binding to the extracellular domain of FGFR1. Solid evidence for quantitative differences in the downstream responses induced by the three ligands is presented. This manuscript will be of interest to biochemists and cell biologists working on receptor tyrosine kinases and general cell signalling across membranes.

Reviewed by eLife

Glutamate helps unmask the differences in driving forces for phase separation versus clustering of FET family proteins in sub-saturated solutions

1. Mrityunjoy Kar
2. Laura T. Vogel
3. Gaurav Chauhan
4. Hannes Ausserwöger
5. Timothy J. Welsh
6. Anjana R. Kamath
7. Tuomas P. J. Knowles
8. Anthony A. Hyman
9. Claus A. M. Seidel
10. Rohit V. Pappu

Reviewed by preLights

Myristoyl’s dual role in allosterically regulating and localizing Abl kinase

1. Svenja de Buhr
2. Frauke Gräter

• Curated by eLife

  eLife assessment

  This is an important study of the mechanism of how binding of the fatty acid myristic acid (MYR) inhibits the activity of the kinase c-Abl, a critical regulator of many cellular processes. While the general aspects of this regulation are known from structure determination and biochemical studies, the exact molecular mechanism and the nature of the allosteric inhibition were not known. The authors use MD simulation to close this gap and provide a detailed mechanistic description of the inhibitory mechanism, although some of the evidence remains incomplete.

Reviewed by eLife

Intracellular Helix-Loop-Helix Domain Modulates Inactivation Kinetics of Mammalian TRPV5 and TRPV6 Channels

1. Lisandra Flores-Aldama
2. Daniel Bustos
3. Deny Cabezas-Bratesco
4. Wendy Gonzalez
5. Sebastian E. Brauchi

• 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

Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein

1. Márton A Simon
2. Iordan Iordanov
3. Andras Szollosi
4. László Csanády

• Curated by eLife

  eLife assessment

  This study uncovers a unique feature of the nucleotide binding domain interface in human CFTR, offering valuable insights into the effects of different non-hydrolytic mutations on CFTR gating. While the evidence presented is solid, a more thorough examination of the non-hydrolytic mutants of zebrafish CFTR for comparison would strengthen the authors' claims. In the current form, more cautious interpretations of some of the data are needed. This study will be of interest to researchers in the fields of cystic fibrosis and proteins in the ATP Binding Cassette (ABC) transporter family.

Reviewed by eLife

Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal

1. Tej Kandola
2. Shriram Venkatesan
3. Jiahui Zhang
4. Brooklyn T Lerbakken
5. Alex Von Schulze
6. Jillian F Blanck
7. Jianzheng Wu
8. Jay R Unruh
9. Paula Berry
10. Jeffrey J Lange
11. Andrew C Box
12. Malcolm Cook
13. Celeste Sagui
14. Randal Halfmann

• Curated by eLife

  eLife assessment

  The authors investigate the mechanism of amyloid nucleation in a cellular system using novel ratiometric measurements, providing fundamental insight into the role of polyglutamine length and the sequence features of glutamine-rich regions in amyloid formation. The problem addressed by this study is very significant and the ability to assess nucleation in cells is of considerable value. The data, as presented and analyzed, are mostly convincing.

Reviewed by eLife

Energy coupling and stoichiometry of Zn2+/H+ antiport by the prokaryotic cation diffusion facilitator YiiP

1. Adel Hussein
2. Shujie Fan
3. Maria Lopez-Redondo
4. Ian Kenney
5. Xihui Zhang
6. Oliver Beckstein
7. David L Stokes

• Curated by eLife

  eLife assessment

  This important and elegant study uses experimental structural data, ion affinity measurements, and computational methods to provide insight into the thermodynamic landscape of cation transporters of the Cation Diffusion Facilitator (CDF) superfamily, together with a detailed structural investigation of the role of the three zinc(II) binding sites of the YiiP family member. Overall, the support for the proposed transport cycle of YiiP is compelling. This work will be of interest to biologists and biophysics who work with membrane transporters.

Reviewed by eLife

Diminishing neuronal acidification by channelrhodopsins with low proton conduction

1. Rebecca Frank Hayward
2. F Phil Brooks
3. Shang Yang
4. Shiqiang Gao
5. Adam E Cohen

• Curated by eLife

  eLife assessment

  This important and compelling study investigates the problem of intracellular acidification induced by commonly-used optogenetic stimulating opsins. The low proton permeability of two high-performance opsins is shown to reduce photostimulated acidification. The findings may be of broad interest in the fields of neuroscience research and optogenetic therapies.

Reviewed by eLife

A comprehensive model of Drosophila epithelium reveals the role of embryo geometry and cell topology in mechanical responses

1. Mohamad Ibrahim Cheikh
2. Joel Tchoufag
3. Miriam Osterfield
4. Kevin Dean
5. Swayamdipta Bhaduri
6. Chuzhong Zhang
7. Kranthi Kiran Mandadapu
8. Konstantin Doubrovinski

• Curated by eLife

  eLife assessment

  Using a novel micropipette-based, minimally invasive approach in combination with theoretical and computational analysis, this important work probes tissue mechanics in the Drosophila embryo. The authors provide compelling evidence for the applicability of their method, which reveals important differences between the mechanical properties on the apical and basal tissue sides. This work should be of broad interest to scientists studying tissue mechanics, membranes, and developmental processes.

Reviewed by eLife