Biophysics

Folding of prestin’s anion-binding site and the mechanism of outer hair cell electromotility

1. Xiaoxuan Lin
2. Patrick R Haller
3. Navid Bavi
4. Nabil Faruk
5. Eduardo Perozo
6. Tobin R Sosnick

• Curated by eLife

  eLife assessment

  This study presents important findings regarding the local dynamics at the anion binding site in the SLC26 transporter prestin that is responsible for electromotility in outer hair cells. The authors reveal critical differences to homologous proteins and thereby provide insight into prestin's unique function. The evidence is generally convincing, although orthogonal evidence would be required to fully support the claims concerning the mechanistic basis for voltage sensitivity.

Reviewed by eLife

Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16

1. Huan Wang
2. Syed RA Rizvi
3. Danni Dong
4. Jiaqi Lou
5. Qian Wang
6. Watanyoo Sopipong
7. Yufeng Su
8. Fares Najar
9. Pratul K Agarwal
10. Frank Kozielski
11. Shozeb Haider

• Curated by eLife

  eLife assessment

  This study presents an important discovery that the RNA synthesis protein of SARS-CoV-2, the virus that is responsible for COVID 19, has fewer mutations and causes limited conformational changes. The evidence supporting the claims is convincing, with robust sequence alignment studies, state-of-the-art protein-protein interaction analysis, and molecular conformational analysis. This work has implications for drug design and will be of broad interest to the general biophysics and structural biology community.

Reviewed by eLife

Computational analysis of long-range allosteric communications in CFTR

1. Ayca Ersoy
2. Bengi Altintel
3. Nurit Livnat Levanon
4. Nir Ben-Tal
5. Turkan Haliloglu
6. Oded Lewinson

• Curated by eLife

  eLife assessment

  This manuscript presents a useful analysis of allosteric communication in the CFTR protein using a coarse-grained dynamic model and characterized the role of disease-causing mutations. The results and analyses are generally solid and validated with available experimental observations. The findings provide comprehensive insights into the allosteric mechanism of this protein.

Reviewed by eLife

Regulation of phage lambda packaging motor-DNA interactions: Nucleotide independent and dependent gripping and friction

1. Brandon Rawson
2. Mariam Ordyan
3. Qin Yang
4. Jean Sippy
5. Michael Feiss
6. Carlos E. Catalano
7. Douglas E. Smith

• Curated by eLife

  eLife assessment

  This fundamental study has major implications that can be paradigm-shifting for our understanding of how the phage lambda DNA motor works and what the precise roles of the TerS and TerL proteins in the motor complex are. The experiments are exceptionally well done, providing compelling evidence for the conclusion of the authors.

Reviewed by eLife

Baited reconstruction with 2D template matching for high-resolution structure determination in vitro and in vivo without template bias

1. Bronwyn A Lucas
2. Benjamin A Himes
3. Nikolaus Grigorieff

• Curated by eLife

  eLife assessment

  This is an important demonstration of how the false-positive rate of high-resolution 2D template matching to find particles of a given target structure in 2D cryo-EM images (2DTM) relates to overfitting the data towards the template. The authors present new methods to measure the amount of model bias that gets introduced in high-resolution features of such maps, with compelling evidence that high-resolution features that are not present in the template can still be reconstructed in 3D from images obtained by 2DTM.

Reviewed by eLife

Dynamic landscape of the intracellular termini of acid-sensing ion channel 1a

1. Megan M Cullinan
2. Robert C Klipp
3. Abigail Camenisch
4. John R Bankston

• Curated by eLife

  eLife assessment

  This valuable study illuminates molecular movements of acid-sensing ion channels by combining advanced chemical biology and biophysical techniques. The evidence for the main claim, lack of interaction of molecular termini, is compelling and challenges prior models. This work is expected to pique interest in the ion channel signaling field, providing a fresh perspective.

Reviewed by eLife

An in silico testbed for fast and accurate MR labeling of orthopedic implants

1. Gregory M Noetscher
2. Peter J Serano
3. Marc Horner
4. Alexander Prokop
5. Jonathan Hanson
6. Kyoko Fujimoto
7. James Brown
8. Ara Nazarian
9. Jerome Ackerman
10. Sergey N Makaroff

• Curated by eLife

  eLife assessment

  This manuscript will provide a valuable method to evaluate the safety of MR in patients with orthopaedic implants, which is required in clinics. A strength of the work is that the in-silicon testbed is solid, based on the widely available human project, and validated. In addition, the toolbox will be open for clinical practice.

Reviewed by eLife

Physical basis of the cell size scaling laws

1. Romain Rollin
2. Jean-François Joanny
3. Pierre Sens

• Curated by eLife

  eLife assessment

  This theoretical work deals with the problem of homeostasis of protein density within cells, relying on the Pump and Leak model. The model makes predictions both for growing and senescent cells, which they compare to experimental data on budding yeast. The work extends previous works and makes biologically-relevant predictions, which will be of interest to both theorists and experimentalists interested in cell physiology.

Reviewed by PREreview, eLife

Approximating Projections of Conformational Boltzmann Distributions with AlphaFold2 Predictions: Opportunities and Limitations

1. Benjamin P. Brown
2. Richard A. Stein
3. Jens Meiler
4. Hassane S. Mchaourab

Reviewed by PREreview

Allosteric regulation of kinase activity in living cells

1. Shivani Sujay Godbole
2. Nikolay V Dokholyan

• Curated by eLife

  eLife assessment

  One of the most promising strategies in development of drugs targeting kinases is provided by using allosteric control that allows specific regulation and study of kinase function without directly targeting the active site. This important paper reviews convincingly the current repertoire of tools for regulating the activity of protein kinases with the ultimate goal of developing novel approaches in treating diseases associated with signal dysregulation.

Reviewed by eLife