Biochemistry

Mediator Subunit MED16 Collaborates with UBP1-TFCP2 to Control Transcriptional Activation or Repression via Promoter Positional Specificity

1. Yuanming Zheng
2. Xiaying Zhao
3. Ming Yang
4. Xinyi Yang
5. Huanzhang Zhu
6. Xiaofei Yu
7. Qiang Zhou
8. Gang Wang

• Curated by eLife

  eLife Assessment

  The characterization of a dissociable Mediator subunit implicated in cellular pathways, particularly lung alveolar function and HIV latency, would be conceptually interesting. The authors have preliminary evidence for a stable Med16 subcomplex that may regulate specific genes. This work is useful in that it points to interactions between Med16 and UBP1, but the evidence is preliminary and incomplete.

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 E Oliver
12. Lars Plate
13. Jonathan P Schlebach

• Curated by eLife

  eLife Assessment

  This important study advances our understanding of how cellular quality control machinery influences cystic fibrosis (CF) drug responsiveness by systematically analyzing the effects of the chaperone calnexin on more than two hundreds of CFTR (cystic fibrosis transmembrane regulator) variants. The evidence supporting the conclusions is convincing, with a comprehensive deep mutational scanning methodology and rigorous quantitative analysis. The findings reveal that calnexin is critical for both CFTR protein expression and corrector drug efficacy in a variant-specific manner, providing invaluable insights that could guide the development of personalized CF therapies. This work will be of significant interest to researchers in protein folding, CF drug development, and genetic disease therapeutics.

Reviewed by eLife

Engineering NIR-sighted bacteria

1. Stefanie SM Meier
2. Michael Hörzing
3. Cornelia Böhm
4. Emma LR Düthorn
5. Heikki Takala
6. René Uebe
7. Andreas Möglich

• Curated by eLife

  eLife Assessment

  This important study establishes bathy phytochromes, a unique class of bacterial photoreceptors that respond to near-infrared light (NIR), as versatile tools for bacterial optogenetics. NIR light is a key control signal in optogenetics due to its deep tissue penetration and the ability to combine with existing red- and blue-light sensitive systems, but thus far, NIR-activated proteins have been poorly characterized. The strength of evidence is convincing, with comprehensive in vitro characterization, modular design strategies, and validation across different hosts, supporting the versatility and potential for these tools in biotechnological applications. This study should advance the fields of optogenetics and photobiology and inspire future work.

Reviewed by eLife

Isolation of functional lysosomes from skeletal muscle

1. Thulasi Mahendran
2. Anastasiya Kuznyetsova
3. Neushaw Moradi
4. David A. Hood

Reviewed by Arcadia Science

Erythrocytosis-inducing PHD2 mutations implicate biological role for N-terminal prolyl-hydroxylation in HIF1α oxygen-dependent degradation domain

1. Cassandra C Taber
2. Wenguang He
3. Geneviève MC Gasmi-Seabrook
4. Mia Hubert
5. Fraser G Ferens
6. Mitsuhiko Ikura
7. Jeffrey E Lee
8. Michael Ohh

• Curated by eLife

  eLife Assessment

  In this valuable study, Taber et al. used a battery of biophysical and structural approaches to characterize the impact of erythrocytosis-related mutations in prolyl hydroxylase domain protein 2 (PHD2). The authors show that PHD2 mutant proteins are destabilized, thus supporting the tenet that dysregulation of PHD2/hypoxia induced factor (HIF) axis underpins erythrocytosis, while providing solid evidence that N-terminal ODD prolyl hydroxylation of HIF is indispensable for these phenotypes. These findings were found to be of interest for researchers focusing on oxygen sensing in homeostasis and pathological states.

Reviewed by eLife

D-serine suppresses one-carbon metabolism by competing with mitochondrial L-serine transport

1. Masataka Suzuki
2. Kenichiro Adachi
3. Pattama Wiriyasermukul
4. Mariko Fukumura
5. Ryota Tamura
6. Yoshinori Hirano
7. Yumi Aizawa
8. Tetsuya Miyamoto
9. Sakiko Taniguchi
10. Masahiro Toda
11. Hiroshi Homma
12. Kohsuke Kanekura
13. Kenji Yasuoka
14. Takanori Kanai
15. Masahiro Sugimoto
16. Shushi Nagamori
17. Masato Yasui
18. Jumpei Sasabe

• Curated by eLife

  eLife Assessment

  This work presents valuable new data on the role of D-Serine and how it competes with its stereoisomer L-Serine to influence metabolism. The work presents a variety of solid experimental data combined with simulated results to investigate the mechanisms focused on one-carbon metabolism, which is relevant for several research fields. However, some claims are only partially supported by data, and critical areas comparing L- vs D-Serine and further mechanistic studies are incomplete. Furthermore, while the work has potential for various fields, the work has only been studied in a limited cell type and context.

Reviewed by eLife

The TTLL10 polyglycylase is stimulated by tubulin glutamylation and inhibited by polyglycylation

1. Steven W Cummings
2. Yan Li
3. Jeffrey O Spector
4. Christopher Kim
5. Antonina Roll-Mecak

• Curated by eLife

  eLife Assessment

  In their study, Cummings et al. provide a valuable advance in understanding the hierarchical regulation of tubulin polyglycylation, demonstrating that TTLL8 initiates monoglycylation which is a prerequisite for TTLL10-mediated polyglycylation. The evidence supporting these mechanistic insights is solid, relying on a compelling combination of purified biochemical assays, mass spectrometry, and microscopy. The work is further valued for revealing an unexpected crosstalk between polyglycylation and polyglutamylation that ensures a balanced post-translational modification landscape for proper cilia function.

Reviewed by eLife

RamanMAE: Masked Autoencoders Enable Efficient Molecular Imaging by Learning Biologically Meaningful Spectral Representations

1. Santosh Kumar Paidi
2. Parul Maheshwari

Reviewed by Arcadia Science

Blue-shifted ancyromonad channelrhodopsins for multiplex optogenetics

1. Elena G Govorunova
2. Oleg A Sineshchekov
3. Hai Li
4. Yueyang Gou
5. Hongmei Chen
6. Shuyuan Yang
7. Yumei Wang
8. Stephen Mitchell
9. Alyssa Palmateer
10. Leonid S Brown
11. François St-Pierre
12. Mingshan Xue
13. John L Spudich

• Curated by eLife

  eLife Assessment

  This important study describes newly identified light-gated ion channel homologs (channelrhodopsins, ChRs) in several protist species, with a primary focus on the biophysical characterization of ChRs of ancyromonads. The authors employed a powerful combination of bioinformatics, manual and automated patch-clamp electrophysiology, absorption spectroscopy, and flash photolysis. Additionally, they evaluated the applicability of the newly discovered anion-conducting ChRs in cortical neurons of mouse brain slices and in living C. elegans worms. The evidence supporting most of the claims is compelling, and this work will be of interest to the microbial rhodopsin community and neuro- and cardioscientists utilizing optogenetics in their research.

Reviewed by eLife

Dock-and-lock binding of SxIP ligands is required for stable and selective EB1 interactions

1. Teresa Almeida
2. Eleanor Hargreaves
3. Tobias Zech
4. Igor Barsukov

• Curated by eLife

  eLife Assessment

  This study provides important insights into how the EBH domain of microtubule end-binding protein 1 (EB1) interacts with SxIP peptides derived from the MACF plus-end tracking protein. The revised manuscript includes convincing ITC and NMR experiments that clarify the role of flanking residues and address the influence of dimerization and cooperativity on binding. While some mechanistic aspects remain difficult to resolve experimentally, the data and analysis now more clearly justify the proposed "dock-and-lock" model and its interpretive value. This work will be of interest to structural biologists and biophysicists studying microtubule-associated protein interactions.

Reviewed by eLife