Biochemistry

Crystal structure and catalytic mechanism of PL35 family glycosaminoglycan lyases with an ultrabroad substrate spectrum

1. Lin Wei
2. Hai-Yan Cao
3. Ruyi Zou
4. Min Du
5. Qingdong Zhang
6. Danrong Lu
7. Xiangyu Xu
8. Yingying Xu
9. Wenshuang Wang
10. Xiu-Lan Chen
11. Yu-Zhong Zhang
12. Fuchuan Li

• Curated by eLife

  eLife Assessment

  This useful manuscript reports on the crystal structures of two glycosaminoglycan (GAG) lyases from the PL35 family, along with in vitro enzyme activity assays and comprehensive structure-guided mutagenesis. The authors have addressed key concerns by incorporating additional docking analyses, validating the role of His188 in alginate degradation, and providing ICP-MS data to examine Mn²⁺ binding. While these improvements enhance the study, the study is incomplete due to the lack of enzyme-substrate complex structures and reliance on modeling which still limit mechanistic insight. Nonetheless, the revised manuscript presents a more complete analysis that will be of interest to specialists in carbohydrate-active enzymes.

Reviewed by eLife

A stress-responsive p38 signaling axis in choanoflagellates

1. Florentine U. Rutaganira
2. Maxwell C. Coyle
3. Maria H.T. Nguyen
4. Iliana Hernandez
5. Alex P. Scopton
6. Arvin C. Dar
7. Nicole King

Reviewed by Life Science Editors Foundation, Arcadia Science

Transcriptome-wide identification of 5-methylcytosine by deaminase and reader protein-assisted sequencing

1. Jiale Zhou
2. Ding Zhao
3. Jinze Li
4. Deqiang Kong
5. Xiangrui Li
6. Renquan Zhang
7. Yuru Liang
8. Xun Gao
9. Yuqiang Qian
10. Di Wang
11. Jiahui Chen
12. Liangxue Lai
13. Yang Han
14. Zhanjun Li

• Curated by eLife

  eLife Assessment

  This potentially useful study introduces an orthogonal approach for detecting RNA modification, without chemical modification of RNA, which often results in RNA degradation and therefore loss of information. Compared to previous versions, the most recent one is improved and sufficiently aligned with the standards of the field to merit consideration by the research community, making the evidence solid according to said standards. Nevertheless, uncertainty regarding false positive and false negative rates remains, as it does for some of the alternative approaches. With more rigorous validation, the approach might be of particular interest for sites in RNA molecules where modifications are rare.

Reviewed by eLife

Simultaneous polyclonal antibody sequencing and epitope mapping by cryo electron microscopy and mass spectrometry

1. Douwe Schulte
2. Marta Šiborová
3. Lukas Käll
4. Joost Snijder

• Curated by eLife

  eLife Assessment

  The paper addresses the problem of optimising the mapping of serum antibody responses against a known antigen. The manuscript describes a method using EM polyclonal epitope mapping to help elucidate endogenous antibodies. The work is interesting and valuable to the fields of immunology and serology, and the strength of evidence to support its findings is considered solid.

Reviewed by eLife

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

1. Adrián Merino-Salomón
2. Jonathan Schneider
3. Leon Babl
4. Jan-Hagen Krohn
5. Marta Sobrinos-Sanguino
6. Tillman Schäfer
7. Juan R. Luque-Ortega
8. Carlos Alfonso
9. Mercedes Jiménez
10. Marion Jasnin
11. Petra Schwille
12. Germán 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, but the evidence to support these exciting claims is currently incomplete, mostly because of the suboptimal "resolution of the toroids", so in the absence of additional experiments, the interpretations would need to be toned down.

Reviewed by eLife

Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike

1. A Sofia F Oliveira
2. Fiona L Kearns
3. Mia A Rosenfeld
4. Lorenzo Casalino
5. Lorenzo Tulli
6. Imre Berger
7. Christiane Schaffitzel
8. Andrew D Davidson
9. Rommie E Amaro
10. Adrian J Mulholland

• Curated by eLife

  eLife Assessment

  This manuscript focuses on understanding if and how the glycosylation of SARS-CoV2 spike protein affects a putative allosteric network of interactions controlled by the binding of a fatty acid. The main conclusion is that glycans do not significantly affect the network of allosteric interactions. This valuable information - albeit mainly consisting of negative results - is based on convincing evidence. It will be of interest to scientists focusing on SARS CoV2 protein structure and dynamics.

Reviewed by eLife

AI-based discovery and cryoEM structural elucidation of a KATP channel pharmacochaperone

1. Assmaa Elsheikh
2. Camden M Driggers
3. Ha H Truong
4. Zhongying Yang
5. John Allen
6. Niel M Henriksen
7. Katarzyna Walczewska-Szewc
8. Show-Ling Shyng

• Curated by eLife

  eLife Assessment

  This important study demonstrates that screening by artificial intelligence can identify relevant novel compounds for interacting with KATP channels. The experimental work is compelling. The broader significance of this work relates to the possibility that KATP channel mutations linked to congenital hyperinsulinism may be effectively rescued to the cell surface with a drug, which could normalize insulin secretion or enhance the effectiveness of existing KATP channel activators such as diazoxide.

Reviewed by eLife

Structure of the Calvin-Benson-Bassham sedoheptulose-1,7-bisphosphatase from the model microalga Chlamydomonas reinhardtii

1. Théo Le Moigne
2. Martina Santoni
3. Lucile Jomat
4. Stéphane D Lemaire
5. Mirko Zaffagnini
6. Nicolas Chéron
7. Julien Henri

• Curated by eLife

  eLife Assessment

  This study provides a valuable structural analysis of the Sedoheptulose-1,7-Bisphosphatase (SBPase) from Chlamydomonas reinhardtii. The data presented are solid and based on X-ray structures of the CrSBPase in an oxidized and reduced state, the authors identify a disulfide bond in close proximity to the dimer interface. They show that the redox-state of the CrSBPase impacts its oligomeric state and might also influence the activity of the protein.

Reviewed by eLife

In vivo exchange of glucose and lactate between photoreceptors and the retinal pigment epithelium

1. Daniel T Hass
2. Elizabeth Giering
3. John YS Han
4. Celia M Bisbach
5. Kriti Pandey
6. Brian M Robbings
7. Thomas O Mundinger
8. Nicholas D Nolan
9. Stephen H Tsang
10. Neal S Peachey
11. Nancy J Philp
12. James B Hurley

• Curated by eLife

  eLife Assessment

  This research is valuable as it investigates metabolic shuttling between photoreceptors and retinal pigment epithelium (RPE) using in vivo infusion techniques and mouse models. The authors find that the retina significantly relies on circulating glucose, with photoreceptors being the primary consumers of glucose, which is convincing. However, the study has incomplete evidence to support the claims that photoreceptors can use lactate as a fuel source, that lactate exported from photoreceptors is utilized by the RPE, and that lactate contributes to the TCA cycle in the RPE. These claims need substantial revision to include potential alternative explanations or perform key experiments.

Reviewed by eLife

Unconventional structure and function of PHD domains from Additional Sex Combs-like proteins

1. CJ Reddington
2. AR Walsh
3. C Göbl
4. PD Mace

Reviewed by Review Commons