Biophysics

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.

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.

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.

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.

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.

eLife assessment

The manuscript describes a set of detailed modeling and experimental studies to disentangle the respective roles of gap junctional electrical vs. metabolic coupling mechanisms in the synchronization of islet activity. This is of interest due to the importance of islet synchronization and generally islet network properties in the regulation of insulin secretion from the pancreas. The significance of the findings was judged to be mostly important and the strength of evidence provided was judged to be mostly solid overall.

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.)

eLife assessment

The manuscript describes valuable theoretical calculations focusing on the structural changes in the photosynthetic reaction center postulated by others based on time-resolved crystallography using X-ray free-electron laser (XFEL) (Dods et al., Nature, 2021). The authors provide solid arguments that calculated changes in redox potential Em and deformations using the XEFL structures may reflect experimental errors rather than real structural changes.

eLife assessment

The authors use a previously described technology of designing soluble transmembrane-targeting peptides, to interfere with the receptor function of the T cell receptor (TCR), which provides useful insights into the molecular mechanism of T cell activation. The designed PITCR peptide has functional effects, but the evidence for the proposed mechanism is still incomplete. With further data to support the conclusion, results from this study will be of interest to those studying the TCR as well as those seeking to use the TCR or its derivatives in synthetic biology studies and immunotherapy.

eLife assessment

This exceptional work substantially advances our understanding of the mechanics of the Reissner's fibre (RF) by performing in-vivo experiments that track and analyze the behavior of the RF when it is cut and the behavior of ciliated cells touching the RF when contact is interrupted. The data is valuable and the conclusions are compelling. The work will be of broad interest to many research communities including developmental neuroscience and cilia biology.