Biophysics

Multiscale effects of perturbed translation dynamics inform antimalarial design

1. Leonie Anton
2. Wenjing Cheng
3. Meseret T. Haile
4. David W. Cobb
5. Xiyan Zhu
6. Leyan Han
7. Emerson Li
8. Anjali Nair
9. Carolyn L. Lee
10. Hangjun Ke
11. Guoan Zhang
12. Emma H. Doud
13. Chi-Min Ho

Reviewed by Rapid Reviews Infectious Diseases

Pharmacologic hyperstabilisation of the HIV-1 capsid lattice induces capsid failure

1. KM Rifat Faysal
2. James C Walsh
3. Nadine Renner
4. Chantal L Márquez
5. Vaibhav B Shah
6. Andrew J Tuckwell
7. Michelle P Christie
8. Michael W Parker
9. Stuart G Turville
10. Greg J Towers
11. Leo C James
12. David A Jacques
13. Till Böcking

• Curated by eLife

  eLife assessment

  In this important study, the authors propose that lenacapavir inhibits HIV-1 replication by inducing "lethal hyperstabilization" of the capsid, based on experiments that clearly demonstrate such an effect at high drug concentrations. Data supporting the model are incomplete at low drug concentrations, and a firm correlation between the in vitro effects and therapeutic mechanism of action has not yet been established.

Reviewed by eLife

Asymmetric framework motion of TCRαβ controls load-dependent peptide discrimination

1. Ana Cristina Chang-Gonzalez
2. Robert J Mallis
3. Matthew J Lang
4. Ellis L Reinherz
5. Wonmuk Hwang

• Curated by eLife

  eLife assessment

  Using extensive atomistic molecular dynamics simulations, the authors analyzed the TCR/pMHC interface with different peptide sequences and protein constructs. The results provide important insights into the catch-bond phenomenon in the context of T-cell activation. In particular, the analysis points to convincing evidence that supports the role of force in further discriminating different peptides during the activation process beyond structural considerations.

Reviewed by eLife

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

Surprising Features of Nuclear Receptor Interaction Networks Revealed by Live Cell Single Molecule Imaging

1. Liza Dahal
2. Thomas GW Graham
3. Gina M Dailey
4. Alec Heckert
5. Robert Tjian
6. Xavier Darzacq

• Curated by eLife

  eLife assessment

  This important study provides data that challenges the standard model that binding of Type 2 Nuclear Receptors to chromatin is limited by the available pool of their common heterodimerization partner Retinoid X Receptor. The evidence supporting the conclusions is compelling, utilizing state-of-the-art single-molecule microscopy. This work will be of broad interest to cell biologists who wish to determine limiting factors in gene regulatory networks.

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