Biophysics

Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching

1. Kexin Zhang
2. Timothy Grant
3. Nikolaus Grigorieff

• Curated by eLife

  eLife Assessment

  This important study builds on previous work from the same authors to present a conceptually distinct workflow for cryo-EM reconstruction that uses 2D template matching to enable high-resolution structure determination of small (sub-50 kDa) protein targets. The paper describes how density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template. However, the evidence described for the claim that this technique improves the alignment of the reconstruction of small complexes compared to standard techniques is incomplete. The authors could better evaluate the effects of model bias on the reconstructed densities, as suggested by reviewer #1.

Reviewed by eLife

In silico design and validation of high-affinity RNA aptamers for SARS-CoV-2 comparable to neutralizing antibodies

1. Yanqing Yang
2. Lulu Qiao
3. Yangwei Jiang
4. Zhiye Wang
5. Dong Zhang
6. Damiano Buratto
7. Liquan Huang
8. Ruhong Zhou

• Curated by eLife

  eLife Assessment

  This valuable study introduces CAAMO, a computational framework that combines structure prediction, in silico mutagenesis, molecular simulations, and energy calculations to design RNA aptamers with improved binding affinity. The computational methodology is solid, demonstrating strong theoretical foundations and systematic integration of multiple prediction techniques. Many of the previously identified methodological weaknesses that limit the strength of support for the computational predictions have been addressed.

Reviewed by eLife

Conformational variability of HIV-1 Env trimer and viral vulnerability

1. Yiwei Cao
2. Wonpil Im

• Curated by eLife

  eLife Assessment

  In this valuable study, the authors conducted an impressive amount of atomistic simulations with a glycosylated HIV-1 envelope glycoprotein (Env) trimer in a realistic asymmetric lipid bilayer. The aim was to probe how Env transmembrane domain, cytoplasmic tail, and membrane environment influence ectodomain orientation and antibody epitope exposure. The simulations convincingly show that ectodomain motion is dominated by tilting relative to the membrane and explicitly demonstrate the role of membrane asymmetry in modulating the protein conformation and orientation, and the results are contextualized well in the revised version. Additional analyses of the authors' deposited MD trajectories could serve as invaluable extensions of this work to probe, for example, for exposure of cryptic epitopes and potential allosteric coupling.

Reviewed by eLife

Optimising the tilt-increment for in situ cryo-electron tomography

1. Maarten W Tuijtel
2. Tomáš Majtner
3. Beata Turoňová
4. Martin Beck

• Curated by eLife

  eLife Assessment

  This convincing contribution addresses a question of practical importance: when collecting tilt-series data, what is the optimal angular step size between successive tilt images? The work provides valuable practical insights into cryo-ET data acquisition by demonstrating that balancing two competing demands - sufficient dose per individual tilt image and fine angular sampling - is essential to achieve high-quality tomographic reconstructions. They demonstrate that tilt-series acquired with finer increments (1-3 degrees) yield superior alignment accuracy and improved template-matching performance,

Reviewed by eLife

RNA Selectively Modulates Activity of Virulent Amyloid PSMα3 and Host Defense LL-37 via Phase Separation and Aggregation Dynamics

1. Bader Rayan
2. Eilon Barnea
3. Rinat Indig
4. Christian F Pantoja
5. Jesse Gayk
6. Yael Lupu-Haber
7. Alexander Upcher
8. Amir Argoetti
9. Jacob Aunstrup Larsen
10. Alexander K Buell
11. Markus Zweckstetter
12. Meytal Landau

• Curated by eLife

  eLife Assessment

  This study presents valuable findings on the differential effects of RNA on the phase separation, aggregation dynamics, and bioactivity of PSMα3 and LL-37. The authors provide solid evidence from complementary biophysical and cell-based experiments that RNA influences peptide assembly and associated in vitro activities. The study is of interest for understanding interactions between amyloidogenic peptides and nucleic acids.

Reviewed by eLife

DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2 and -3

1. Crystal R Noell
2. Tzu-Chen Ma
3. Rui Jiang
4. Scott A McKinley
5. William O Hancock

• Curated by eLife

  eLife Assessment

  The authors use convincing methodology to investigate the detachment and reattachment kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel to the microtubule. The conclusions drawn from the valuable experiments as well as the overall interpretation of the results are fully supported by the presented data.

Reviewed by eLife

Heterotypic interfacial tension between oncogenic and wild-type populations forms the mechanical basis of tissue-specific oncogenesis in epithelia

1. Amrapali Datta
2. Phanindra Dewan
3. Aswin Anto
4. Tanya Chhabra
5. Tanishq Tejaswi
6. Sindhu Muthukrishnan
7. Akshar Rao
8. Sumantra Sarkar
9. Medhavi Vishwakarma

• Curated by eLife

  eLife Assessment

  This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This work provides convincing evidence, supported by pharmacological perturbations and numerical simulations using the vertex model, that the principle of "high heterotypic interfacial tension" that appears to drive cell sorting and tissue segregation in embryonic models similarly applies to cancer cell behaviour.

Reviewed by eLife

Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants

1. Richard J Lindsay
2. Abhilash Sahoo
3. Rafael Giordano Viegas
4. Vitor BP Leite
5. Philip A Wigge
6. Sonya M Hanson

• Curated by eLife

  eLife Assessment

  In this potentially valuable computational study, the authors conducted extensive atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating temperature-responsive structural and condensation behavior. Despite considerable improvements in the revised manuscript, the level of evidence is considered incomplete, since several of the supplementary observables introduced to support the revised claim indicate that the variants studied are not statistically distinguishable within the reported replicate uncertainty.

Reviewed by eLife

Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug

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

Reviewed by Rapid Reviews Infectious Diseases

Lenacapavir-induced Lattice Hyperstabilization is Central to HIV-1 Capsid Failure at the Nuclear Pore Complex and in the Cytoplasm

1. Arpa Hudait
2. Ryan C Burdick
3. Ellie K Bare
4. Vinay K Pathak
5. Gregory A Voth

• Curated by eLife

  eLife Assessment

  This study investigates how the HIV inhibitor lenacapavir influences capsid mechanics and interactions with the nuclear pore complex. It provides important insights into how drug-induced hyperstabilization of the viral shell can compromise its structural integrity during nuclear entry. The modeling is technically sophisticated, and the analyses provide convincing support for the mechanistic conclusions.

Reviewed by eLife