Biophysics

Synthetic analysis of chromatin tracing and live-cell imaging indicates pervasive spatial coupling between genes

1. Christopher H Bohrer
2. Daniel R Larson

• Curated by eLife

  eLife Assessment:

  The authors use their expertise in live-cell imaging and mathematical modeling to explore the relationship between chromatin structure, gene positioning and transcriptional co-regulation, using two publicly available datasets encompassing chromatin tracing and transcriptional activity. The resulting analysis reveals a weak association between transcription and proximity, but needs more statistical validation to strengthen the validity of the conclusions. With some clarifications and revisions, several findings, such as coupling of spatiotemporal positioning with activity, in-depth analysis of existing imaging/ChIP-seq datasets, could make this work impactful to both specialists and non-specialists.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Noncovalent antibody catenation on a target surface greatly increases the antigen-binding avidity

1. Jinyeop Song
2. Bo-Seong Jeong
3. Seong-Woo Kim
4. Seong-Bin Im
5. Seonghoon Kim
6. Chih-Jen Lai
7. Wonki Cho
8. Jae U Jung
9. Myung-Ju Ahn
10. Byung-Ha Oh

• Curated by eLife

  eLife Assessment:

  The authors sought to enhance antibody binding to target antigens via reversible catenation, as an alternative to affinity maturation, beginning by computationally establishing parameters under which this type of binding enhancement via avidity effects would occur, and then following up with proof-of-principle experiments. While computational predictions and experiments are in excellent agreement, some controls that would further strengthen data interpretation are lacking. If generally applicable, the approach would accelerate efforts to develop antibodies with enhanced binding potency relative to their progenitors, applicable to any area of research employing antibodies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Interpreting the molecular mechanisms of disease variants in human transmembrane proteins

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

Reviewed by Biophysics Colab

Structural and thermodynamic analyses of the β-to-α transformation in RfaH reveal principles of fold-switching proteins

1. Philipp K Zuber
2. Tina Daviter
3. Ramona Heißmann
4. Ulrike Persau
5. Kristian Schweimer
6. Stefan H Knauer

• Curated by eLife

  Evaluation Summary:

  This is an interesting and timely paper that presents thermodynamic and structural (NMR) analyses of six KOW domains from the NusG superfamily of transcription factors. The authors identify a second fold-switching member of the NusG superfamily, VcRfaH, and investigate the physical basis of this fold-switching transition. The authors also compare the thermodynamic and structural properties of six fold-switching and single-folding KOW domains from different organisms, and show that fold-switching domains are less thermodynamically stable than their single-folding counterparts. This work will be of great interest for scientists in the fields of protein folding (theory and experiment), structural biophysics, and advanced protein NMR spectroscopy.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Activation-pathway transitions in human voltage-gated proton channels revealed by a non-canonical fluorescent amino acid

1. Esteban Suárez-Delgado
2. Maru Orozco-Contreras
3. Gisela E Rangel-Yescas
4. Leon D Islas

• 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

Molecular mechanism of active Cas7-11 in processing CRISPR RNA and interfering target RNA

1. Hemant N Goswami
2. Jay Rai
3. Anuska Das
4. Hong Li

• Curated by eLife

  Evaluation Summary:

  This manuscript is a timely contribution to the CRISPR/Cas field: the mode of function of the type III-E Cas7-11 CRISPR-Cas system. This is an RNA-guided RNA targeting system only characterized last year. In contrast to Cas13 systems, Cas7-11 does not possess collateral damaging activity, hence does not show cytotoxicity when introduced into human cells. These are highly desirable traits in practical applications. High resolution mechanistic studies would be essential for driving the further development of Cas7-11 based biotechnology applications.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Computational design of peptides to target NaV1.7 channel with high potency and selectivity for the treatment of pain

1. Phuong T Nguyen
2. Hai M Nguyen
3. Karen M Wagner
4. Robert G Stewart
5. Vikrant Singh
6. Parashar Thapa
7. Yi-Je Chen
8. Mark W Lillya
9. Anh Tuan Ton
10. Richard Kondo
11. Andre Ghetti
12. Michael W Pennington
13. Bruce Hammock
14. Theanne N Griffith
15. Jon T Sack
16. Heike Wulff
17. Vladimir Yarov-Yarovoy

• Curated by eLife

  eLife assessment

  The authors of this manuscript set out to improve on a peptide, ProTxII, which had been previously put forward as a promising blocker of Nav1.7 channels and thus offers a possible non-opiate way to block pain. They develop a useful computational workflow that is based on in silico manipulations of the interaction of ProTxII with a Na channel structure determined previously and evaluation of the predicted mutations with electrophysiology. The authors succeed in producing two peptides with improved selectivity for Nav1.7 over other subtypes and capable of producing ion channel block at low concentrations and the experimental evidence presented is solid, and the general applicability of the method is compelling.

Reviewed by eLife

A tug of war between filament treadmilling and myosin induced contractility generates actin rings

1. Qin Ni
2. Kaustubh Wagh
3. Aashli Pathni
4. Haoran Ni
5. Vishavdeep Vashisht
6. Arpita Upadhyaya
7. Garegin A Papoian

• Curated by eLife

  Evaluation Summary:

  This important paper uses molecular simulations to explain how actomyosin networks transition from small clusters to the cortex or ring-shaped actin networks. The authors provide compelling evidence that variation in filament turnover rate and myosin concentration triggers a phase transition of these networks. The predictions of this model are consistent with observations made in T cells, where actin ring formation can be induced following their activation by antibodies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

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

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

Targeting RNA:protein interactions with an integrative approach leads to the identification of potent YBX1 inhibitors

1. Krystel El Hage
2. Nicolas Babault
3. Olek Maciejak
4. Bénédicte Desforges
5. Pierrick Craveur
6. Emilie Steiner
7. Juan Carlos Rengifo-Gonzalez
8. Hélène Henrie
9. Marie-Jeanne Clement
10. Vandana Joshi
11. Ahmed Bouhss
12. Liya Wang
13. Cyril Bauvais
14. David Pastré

• Curated by eLife

  Evaluation Summary:

  Protein-RNA interactions are involved in many diseases and targeting them with drugs can be valuable. Because protein-RNA complexes are considered difficult to target both computationally and experimentally, an integrated computational-experimental approach to solve this limitation is introduced. The approach is demonstrated by targeting the mRNA-binding protein YB-1, which works remarkably well. Inhibitors in the micromolar range are detected, including a previously approved drug. The main strength here is the proof of concept that protein-RNA interactions are targetable. However, additional data are required to support the central claims of the paper.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife