Biophysics

Structure and Cl- Conductance Properties of the Open State of Human CFTR

1. Zhi-Wei Zeng
2. Christopher E Ing
3. Régis Pomès

• Curated by eLife

  eLife Assessment

  This important study reports a detailed computational analysis of the CFTR ion channel's permeation mechanism, advancing our understanding of its structure-function relationship. The conclusions are based on extensive molecular dynamics simulations and thorough analysis, but the use of an approximate chloride ion model, known to underestimate key ion-protein interactions, leaves them incomplete without experimental or alternative computational validation. The work will be of interest to biophysicists working on CFTR and cystic fibrosis.

Reviewed by eLife

A thermodynamic framework for nonequilibrium self-assembly and force morphology tradeoffs in branched actin networks

1. Elisabeth Rennert
2. Suriyanarayanan Vaikuntanathan

• Curated by eLife

  eLife Assessment

  Rennert et al. developed a valuable thermodynamic framework to study the force response of branched actin networks from the crucial and unexplored perspective of energetic cost. They used the fact that the entropy production rate must be positive to derive inequalities that set limits on the maximum force produced by branched actin networks, and speculate that the dissipative cost beyond that required to move the load may be necessary to maintain an adaptive steady state. This work is highly innovative, but remains incomplete until the hypotheses of the model are better justified and the conclusions about the dissipative cost of the system are better established.

Reviewed by eLife

A conformational fingerprint for amyloidogenic light chains

1. Cristina Paissoni
2. Sarita Puri
3. Luca Broggini
4. Manoj K Sriramoju
5. Martina Maritan
6. Rosaria Russo
7. Valentina Speranzini
8. Federico Ballabio
9. Mario Nuvolone
10. Giampaolo Merlini
11. Giovanni Palladini
12. Shang-Te Danny Hsu
13. Stefano Ricagno
14. Carlo Camilloni

• Curated by eLife

  eLife Assessment

  This study addresses an important and longstanding question regarding the molecular mechanism of protein misfolding in Ig light chain (LC) amyloidosis (AL), a life-threatening condition. By combining advanced techniques, including small-angle X-ray scattering, molecular dynamics simulations, and hydrogen-deuterium exchange mass spectrometry, the authors provide convincing evidence that the "H state" distinguishes amyloidogenic from non-amyloidogenic LCs. These findings not only offer novel insights into LC structural dynamics but also hold promise for guiding therapeutic strategies in amyloidosis and will be of particular interest to structural biologists, biophysicists, and many others working on amyloid diseases.

Reviewed by eLife

Reliable protein–protein docking with AlphaFold, Rosetta, and replica exchange

1. Ameya Harmalkar
2. Sergey Lyskov
3. Jeffrey J Gray

• Curated by eLife

  eLife Assessment

  The authors report how a previously published method, ReplicaDock, can be used to improve predictions from AlphaFold-multimer (AFm) for protein docking studies. The level of improvement is modest for cases where AFm is successful; for cases where AFm is not as successful, the improvement is more significant, although the accuracy of prediction is also notably lower. The evidence for the ReplicaDock approach being more predictive than AFm is particularly convincing for the antibody-antigen test case. Overall, the study makes a valuable contribution by combining data- and physics-driven approaches.

Reviewed by eLife

Flexibility in PAM recognition expands DNA targeting in xCas9

1. Kazi A Hossain
2. Lukasz Nierzwicki
3. Modesto Orozco
4. Jacek Czub
5. Giulia Palermo

• Curated by eLife

  eLife Assessment

  This manuscript describes a fundamental investigation of the functioning of Cas9 and in particular on how variant xCas9 expands DNA targeting ability by an increase-flexibility mechanism. The authors provide compelling evidence to support their mechanistic models and the relevance of flexibility and entropy in recognition. This work can be of interest to a broad community of structural biophysicists, computational biologists, chemists, and biochemists.

Reviewed by eLife

PROTAC-induced protein structural dynamics in targeted protein degradation

1. Kingsley Y Wu
2. Ta I Hung
3. Chia-en A Chang

• Curated by eLife

  eLife Assessment

  This study provides important computational insights into the dynamics of PROTAC-induced degradation complexes, offering a convincing demonstration that differences in degradation efficacy can be linked to linker properties. The analyses address reproducibility considerations comprehensively, reinforcing the study's conclusions. Overall, these findings are significant for advancing cancer treatments and will be of broad interest to both biochemists and biophysicists.

Reviewed by eLife

Tension-induced suppression of allosteric conformational changes explains coordinated stepping of kinesin-1

1. Tsukasa Makino
2. Ryo Kanada
3. Teppei Mori
4. Ken-ichi Miyazono
5. Yuta Komori
6. Haruaki Yanagisawa
7. Shoji Takada
8. Masaru Tanokura
9. Masahide Kikkawa
10. Michio Tomishige

Reviewed by Review Commons

Mechanical stresses govern myoblast fusion and myotube growth

1. Yoann Le Toquin
2. Sushil Dubey
3. Aleksandra Ardaševa
4. Lakshmi Balasubramaniam
5. Emilie Delaune
6. Valérie Morin
7. Amin Doostmohammadi
8. Christophe Marcelle
9. Benoît Ladoux

Reviewed by preLights

Cell cycle and age-related modulations of mouse chromosome stiffness

1. Ning Liu
2. Wenan Qiang
3. Philip W Jordan
4. John F Marko
5. Huanyu Qiao

• Curated by eLife

  eLife Assessment

  This valuable paper describes the stiffness of meiotic chromosomes in both oocytes and spermatocytes. The authors identify differences in stiffness between meiosis I and II chromosomes, as well as an age-dependent increase in stiffness in meiosis I (and meiosis II) chromosomes, results that are highly significant for the field of chromosome biology. The report is, however, mostly descriptive and the mechanisms underlying age-dependent changes in chromosome stiffness remain unclear. The evidence suggesting that changes in stiffness are independent of cohesin, which is known to deteriorate with age, is still incomplete.

Reviewed by eLife