Biophysics

Predicting the Sequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins

1. Sanbo Qin
2. Huan-Xiang Zhou

• Curated by eLife

  eLife assessment

  In this useful study, a solid machine learning approach based on a broad set of systems to predict the R2 relaxation rates of residues in intrinsically disordered proteins (IDPs) is described. The ability to predict the patterns of R2 will be helpful to guide experimental studies of IDPs. A potential weakness is that the predicted R2 values may include both fast and slow motions, thus the predictions provide only limited new physical insights into the nature of the underlying protein dynamics, such as the most relevant timescale.

Reviewed by eLife

PUFA stabilizes a conductive state of the selectivity filter in IKs channels

1. Alessia Golluscio
2. Jodene Eldstrom
3. Jessica J Jowais
4. Marta E Perez-Rodriguez
5. Kevin P Cunningham
6. Alicia de la Cruz
7. Xiaoan Wu
8. Valentina Corradi
9. D Peter Tieleman
10. David Fedida
11. H Peter Larsson

• Curated by eLife

  eLife assessment

  This manuscript reveals an important mechanism of KCNQ1/IKs channel gating and PUFA modulation of this mechanism. This mechanism is supported by convincing single channel recordings, macroscopic current recordings and mutational analyses. These findings are of importance to the ion channel field and possibly future therapeutic applications.

Reviewed by eLife

N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine

1. Chuchu Wang
2. Chunyu Zhao
3. Xiao Hu
4. Jiali Qiang
5. Zhenying Liu
6. Jinge Gu
7. Shengnan Zhang
8. Dan Li
9. Yaoyang Zhang
10. Jacqueline Burré
11. Jiajie Diao
12. Cong Liu

• Curated by eLife

  eLife assessment

  In this useful study, the authors show that N-acetylation of synuclein increases clustering of synaptic vesicles in vitro and that this effect is mediated by enhanced interaction with lysophosphatidylcholine. While the evidence for enhanced clustering is largely solid, the biological significance remains unclear.

Reviewed by eLife

Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2

1. Siyu Chen
2. Tamar Basiashvili
3. Joshua Hutchings
4. Marta Sanz Murillo
5. Amalia Villagran Suarez
6. Jaime Alegrio Louro
7. Andres E Leschziner
8. Elizabeth Villa

• Curated by eLife

  eLife assessment

  In this manuscript, Chen et al. used cryo-ET and in vitro reconstituted system to demonstrate that the autoinhibited form of LRRK2 can also assemble into filaments on the microtubule surface, with a new interface involving the N-terminal repeats that were disordered in the previous active-LRRK2 filament structure. The structure obtained in this study is the highest resolution of LRRK2 filaments done by subtomogram averaging, representing a major technical advance compared to the previous paper from the same group. This is an important study, especially considering the pharmacological implications of the effect of inhibitors of the protein. The strengths of the data are convincing, but the study would be considerably strengthened if the authors addressed several discrepancies relating to their earlier work, and explored the physiological significance of the new interfaces and the incomplete decoration of microtubules described here.

Reviewed by eLife

Point set registration for combining fluorescence microscopy methods

1. Ivo Severins
2. Chirlmin Joo
3. John van Noort

Reviewed by Arcadia Science

PROTAC-induced Protein Functional 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. The findings are solid and hold significant implications for advancing cancer treatments, particularly for breast and prostate cancers. However, the major conclusions of the work could be strengthened with a more thorough analysis. This work will be of broad interest to both biochemists and biophysicists.

Reviewed by eLife

Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting

1. Yangyu Wu
2. Yangyang Yan
3. Youshan Yang
4. Shumin Bian
5. Alberto Rivetta
6. Ken Allen
7. Fred J Sigworth

• Curated by eLife

  eLife assessment

  This important manuscript presents several structures of the Kv1.2 voltage-gated potassium channel, based on state-of-the-art cryoEM techniques and algorithms. The authors present solid evidence for structures of an inactivating mutant of Kv1.2, DTX-bound Kv1.2 and of Kv1.2 in potassium-free solution (with presumably sodium ions bound within the selectivity filter). These structures advance our knowledge of the molecular basis of the slow inactivation process of potassium channels.

Reviewed by eLife

Hypersensitivity of the vimentin cytoskeleton to net-charge states and Coulomb repulsion

1. Bret A Unger
2. Chun Ying Wu
3. Alexander A Choi
4. Changdong He
5. Ke Xu

• Curated by eLife

  eLife assessment

  This valuable study provides new insight into the disassembly of vimentin filaments and the dependence of this mechanism on net charge, albeit with incomplete evidence. In particular, the experimental replicates are limited (in most cases n=1), there is a lack of quantitative analysis to substantiate claims, inconsistency of the proposed mechanisms with previously published work, and lack of biochemical evidence supporting the observations in cells. Addressing these concerns would strengthen the manuscript and help support the proposed hypothesis on vimentin disassembly.

Reviewed by eLife

Spiral-eyes: A soft active matter model of in vivo corneal epithelial cell migration

1. Kaja Kostanjevec
2. Rastko Sknepnek
3. Jon Martin Collinson
4. Silke Henkes

Reviewed by preLights

Unveiling Cas8 Dynamics and Regulation within a transposon-encoded Cascade-TniQ Complex

1. Amun Patel
2. Souvik Sinha
3. Pablo Arantes
4. Giulia Palermo

Reviewed by PREreview