Biophysics

Interplay between charge distribution and DNA in shaping HP1 paralog phase separation and localization

1. Tien M Phan
2. Young C Kim
3. Galia T Debelouchina
4. Jeetain Mittal

• Curated by eLife

  eLife assessment

  This valuable study substantially advances our understanding of molecular mechanisms driving the phase separation behavior of HP1 paralogs. The evidence supporting the conclusions is convincing, with rigorous and well-designed computational simulations. The work will be of broad interest to biophysicists and biochemists.

Reviewed by eLife

Structural basis for the preservation of a subset of topologically associating domains in interphase chromosomes upon cohesin depletion

1. Davin Jeong
2. Guang Shi
3. Xin Li
4. D Thirumalai

• Curated by eLife

  eLife assessment

  This valuable study, of interest for students of the biology of genomes, uses simulations in combination with published data to examine how many TADs remain after cohesin depletion. The authors suggest that a significant subset of chromosome conformations do not require cohesin, and that knowledge of specific epigenetic states can be used to identify regions of the genome that still interact in the absence of cohesin. The theoretical approaches and quantitative analysis are state-of-the-art, and the data quality and strength of the conclusions are convincing, but it is unfortunately still unclear whether physical boundaries (of domains?) in the model appear to be a consequence of preserved TADs, or whether preserved TADs are caused by the physical boundaries.

Reviewed by eLife

Raman microscopy of cryofixed biological specimens for high-resolution and high-sensitivity chemical imaging

1. Kenta Mizushima
2. Yasuaki Kumamoto
3. Shoko Tamura
4. Masahito Yamanaka
5. Kentaro Mochizuki
6. Menglu Li
7. Syusuke Egoshi
8. Kosuke Dodo
9. Yoshinori Harada
10. Nicholas I. Smith
11. Mikiko Sodeoka
12. Hideo Tanaka
13. Katsumasa Fujita

Reviewed by Arcadia Science

The molecular basis of Abelson kinase regulation by its αI-helix

1. Johannes Paladini
2. Annalena Maier
3. Judith Maria Habazettl
4. Ines Hertel
5. Rajesh Sonti
6. Stephan Grzesiek

• Curated by eLife

  eLife assessment

  This manuscript describes an important NMR investigation of allosteric interactions within Abl kinase. The authors identify helix I as a major element that couples the Abl active site with the myristate-binding pocket. The convincing findings have implications for understanding Abl kinase activation and how to target Abl kinase in diseases.

Reviewed by eLife

The positioning mechanics of microtubule asters in Drosophila embryo explants

1. Jorge de-Carvalho
2. Sham Tlili
3. Timothy E Saunders
4. Ivo A Telley

• Curated by eLife

  eLife assessment

  This manuscript utilizes a Drosophila explant system and modeling to provide important insights into the mechanism of microtubule aster positioning. Although the intellectual framework of aster positioning has been worked out by the same authors in their previous work, this study provides additional solid evidence to solidify their model.

Reviewed by eLife

Biophysical mechanism of ultrafast helical twisting contraction in the giant unicellular ciliate Spirostomum ambiguum

1. L. X. Xu
2. M. S. Bhamla

Reviewed by Arcadia Science

Explicit ion modeling predicts physicochemical interactions for chromatin organization

1. Xingcheng Lin
2. Bin Zhang

• Curated by eLife

  eLife assessment

  The authors have developed a compelling coarse-grained simulation approach for nucleosome-nucleosome interactions within a chromatin array. The data presented are solid and provide new insights that allow for predictions of how chromatin interactions might occur in vivo. The tools presented herein will be valuable for the chromosome biology field.

Reviewed by eLife

Tracing the substrate translocation mechanism in P-glycoprotein

1. Theresa Gewering
2. Deepali Waghray
3. Kristian Parey
4. Hendrik Jung
5. Nghi NB Tran
6. Joel Zapata
7. Pengyi Zhao
8. Hao Chen
9. Dovile Januliene
10. Gerhard Hummer
11. Ina Urbatsch
12. Arne Moeller
13. Qinghai Zhang

• Curated by eLife

  eLife assessment

  P-glycoprotein is a major ABC-transporter that exports drugs used in chemotherpay and effects the pharmacokinetics of other drugs. Here the authors have determined cryo-EM structures of drug complexes in previously unforeseen outward-facing conformations. These convincing findings are mechanistically important and reveal potential regions to be exploited by rational-based drug design.

Reviewed by eLife

CryoEM structures of the human CLC-2 voltage-gated chloride channel reveal a ball-and-chain gating mechanism

1. Mengyuan Xu
2. Torben Neelands
3. Alexander S Powers
4. Yan Liu
5. Steven D Miller
6. Grigore D Pintilie
7. J Du Bois
8. Ron O Dror
9. Wah Chiu
10. Merritt Maduke

• Curated by eLife

  eLife assessment

  This study examines the human voltage-gated chloride channel CLC-2. A combination of cryo-EM, electrophysiology, and computational analysis provides compelling support for a "ball and chain" mechanism of inactivation. This and other findings regarding the gating and inhibition mechanisms of the channel are of fundamental interest to ion channel physiologists.

Reviewed by eLife

Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM

1. Cathrine Bergh
2. Urška Rovšnik
3. Rebecca Howard
4. Erik Lindahl

• Curated by eLife

  eLife assessment

  The authors use a combination of structural and MD simulation approaches to characterize phospholipid interactions with the pentameric ligand-gated ion channel, GLIC. The general agreement between structures and simulations increases confidence in the description of the lipid interaction poses and provides a solid basis for the prediction of a state-dependent interaction site where lipids could dynamically modulate channel gating. The results will be very useful to understand the nature of phospholipid interactions with pentameric ligand-gated ion channels, although the functional or structural significance of these lipid interactions remains to be verified.

Reviewed by eLife