Biochemistry

Chronobot: Deep learning guided time-resolved cryo-EM captures molecular choreography of RecA in homology search

1. Märt-Erik Mäeots
2. Simon Tupin
3. Mohammad M. N. Esfahani
4. Juan B. Rodriguez Molina
5. Julie A. Clapperton
6. Aran Amin
7. Albane Imbert
8. Radoslav I. Enchev

Reviewed by PREreview

Crosslinking by ZapD drives the assembly of short FtsZ filaments into toroidal structures in solution

1. Adrián Merino-Salomón
2. Jonathan Scheneider
3. Leon Babl
4. Jan-Hagen Krohn
5. Marta Sobrinos-Sanguino
6. Tillman Schaefer
7. Juan Ramon Luque-Ortega
8. Carlos Alfonso
9. Mercedes Jiménez
10. Marion Jasnin
11. Petra Schwille
12. German Rivas

• Curated by eLife

  eLife Assessment

  The formation of the Z-ring at the time of bacterial cell division interests researchers working towards understanding cell division across all domains of life. The manuscript by Jasnin et al reports the cryoET structure of toroid assembly formation of FtsZ filaments driven by ZapD as the cross linker. The findings are important and have the potential to open a new dimension in the field, and the evidence to support these exciting claims is solid.

Reviewed by eLife

Concatenated Modular BK Channel Constructs Reveal Divergent Stoichiometry in Gating Control by LRRC26 (γ1), Pore, and Selectivity Filter

1. Guanxing Chen
2. Qin Li
3. Jiusheng Yan

• Curated by eLife

  eLife Assessment

  In this important contribution, Yan and colleagues describe a powerful and compelling strategy to generate concatamers of the BK channel and their fusion constructs with the auxiliary gamma subunits, which allows exploring contributions of individual subunits of the tetrameric channel to its gating and the study of heteromeric channel complexes of defined composition. Distinct examples are presented, which illustrate great diversity in the stoichiometric control of BK channel gating, depending on the site and nature of molecular perturbations. The molecular approaches could be extended to other membrane proteins whose N and C termini face opposite sides of the membrane.

Reviewed by eLife

General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants

1. Austin Tedman
2. John A Olson
3. Minsoo Kim
4. Catherine Foye
5. JaNise J Jackson
6. Eli F McDonald
7. Andrew G McKee
8. Karen Noguera
9. Charles P Kuntz
10. Jens Meiler
11. Kathryn Oliver
12. Lars Plate
13. Jonathan P Schlebach

• Curated by eLife

  eLife Assessment

  This important study systematically investigates the effects of calnexin, an endoplasmic reticulum chaperone, on the drug response of approximately 230 disease-causing variants of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Through deep mutational scanning, interactome profiling, and functional assays, the findings provide convincing evidence that calnexin significantly influences both CFTR expression and the efficacy of corrector drugs in a variant-specific manner. These insights advance our understanding of how cellular quality control machinery shapes the pharmacological responsiveness of CFTR variants, which are broadly relevant for researchers in protein folding and genetic disease therapeutics.

Reviewed by eLife

A miniaturized, high-throughput buffer-centric method for protein solubility screening

1. Adrian Svoboda
2. Marina Molineris
3. Tomáš Pluskal
4. Teo Hebra

Reviewed by Arcadia Science

Allosteric modulation of dimeric GPR3 by ligands in the dimerization interface

1. Zeming Qiu
2. Wei Wang
3. Yingying Nie
4. Junxiang Lin
5. Beimeng Zhang
6. Haonan Xing
7. Sanduo Zheng

• Curated by eLife

  eLife Assessment

  Qiu et al. present multiple dimeric structures of GPR3, which reveal the binding mode of the inverse agonist AF64394. The findings provide important insights into the regulation of GPCR3 and potentially other related orphan GPCRs. The authors present convincing evidence of their claims through thoughtful analysis of their cryo-EM structures, mutagenesis, and cell-based assays. This work will be of interest to GPCR investigators, especially those studying the signaling of orphan receptors.

Reviewed by eLife

Inherited CDA-I disease: anemia-associated mutations disrupt CDIN1-Codanin1 complex

1. Martin Stojaspal
2. Tomáš Brom
3. Ivona Nečasová
4. Tomáš Janovič
5. Pavel Veverka
6. Naina Verma
7. Lukáš Uhrík
8. Lenka Hernychova
9. Ctirad Hofr

Reviewed by Review Commons

Amyloid-β fibrils accumulated in preeclamptic placentas suppress syncytialization of cytotrophoblasts

1. Kaho Nishioka
2. Midori Ikezaki
3. Naoyuki Iwahashi
4. Miyu Arakawa
5. Momo Fukushima
6. Noa Mori
7. Mika Mizoguchi
8. Yuko Horiuchi-Tanizaki
9. Megumi Fujino
10. Takami Tomiyama
11. Yoshito Ihara
12. Kenji Uchimura
13. Kazuhiko Ino
14. Kazuchika Nishitsuji

Reviewed by Review Commons

A high-resolution analysis of arrestin2 interactions responsible for CCR5 endocytosis

1. Ivana Petrovic
2. Samit Desai
3. Polina Isaikina
4. Layara Akemi Abiko
5. Anne Spang
6. Stephan Grzesiek

• Curated by eLife

  eLife Assessment

  The authors investigate arrestin2-mediated CCR5 endocytosis in the context of clathrin and AP2 contributions. Using an extensive set of NMR experiments, and supported by microscopy and other biophysical assays, the authors provide convincing data on the roles of AP2 and clathrin in CCR5 endocytosis. This important work will appeal to an audience beyond those studying chemokine receptors, including those studying GPCR regulation and trafficking. The distinct role of AP2 and not clathrin will be of particular interest to those studying GPCR internalization mechanisms.

Reviewed by eLife

Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes

1. Janelle JY Chuah
2. Madalena R Daugherty
3. David M Smith

• Curated by eLife

  eLife Assessment

  This valuable manuscript describes cryo-EM structures of archaeal proteasomes that reveal insights into how occupancy of binding pockets on the 20S proteasome regulates proteasome gating. The evidence supporting these claims is convincing, although the extrapolation of these findings to the more complex eukaryotic proteasome may prove challenging. This work will be of high interest to researchers interested in proteasome structure and regulation.

Reviewed by eLife