Biochemistry

Beyond the Active Site: The addition of a remote loop reveals a new complex biological function for chitinase enzymes

1. Dan Kozome
2. Adnan Sljoka
3. Paola Laurino

Reviewed by Arcadia Science

The catalytic mechanism of the RNA methyltransferase METTL3

1. Ivan Corbeski
2. Pablo Andrés Vargas-Rosales
3. Rajiv Kumar Bedi
4. Jiahua Deng
5. Dylan Coelho
6. Emmanuelle Braud
7. Laura Iannazzo
8. Yaozong Li
9. Danzhi Huang
10. Mélanie Ethève-Quelquejeu
11. Qiang Cui
12. Amedeo Caflisch

• Curated by eLife

  eLife assessment

  This important study combines experimental and computational data to address crucial aspects of RNA methylation by a vital RNA methyltransferase (MTase). The authors have provided compelling, strong evidence, utilizing well-established techniques, to elucidate aspects of the methyl transfer mechanism of methyltransferase-like protein 3 (METTL3), which is a part of the METTL3-14 complex. This work will be of broad interest to biochemists, biophysicists, and cell biologists alike.

Reviewed by eLife

Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens

1. Veronica Teresa Ober
2. George Boniface Githure
3. Yuri Volpato Santos
4. Sidney Becker
5. Gabriel Moya Munoz
6. Jérôme Basquin
7. Frank Schwede
8. Esben Lorentzen
9. Michael Boshart

• Curated by eLife

  eLife assessment

  This landmark study sheds light on a long-standing puzzle in Protein kinase A activation in Trypanosoma. Extensive experimental work provides exceptional evidence for the conclusions of the work, which represents a significant advancement in our understanding of the molecular mechanism of cyclic nucleotide binding domains. The work is relevant for researchers with interests in kinases and their mechanistic study.

Reviewed by eLife

Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant

1. Patsy R. Tomlinson
2. Rachel Knox
3. Olga Perisic
4. Helen C. Su
5. Gemma V. Brierley
6. Roger L. Williams
7. Robert K. Semple

• Curated by eLife

  eLife assessment

  The authors identify new mechanisms that link a PIK3R1 mutant to cellular signaling and division in Activated PI3 Kinase Delta Syndrom 1 and 2 (APDS1/2). The conclusion that this mutant serves as a dominant negative form of the protein, impacting PI3K complex assembly and IRS/AKT signaling, is important, and the evidence from constitutive and inducible systems in cultured cells is convincing. Nevertheless, there are several limitations relating to differences between cell lines and expression systems, as well as more global characterization of the protein interaction landscape, which would further enhance the work.

Reviewed by eLife

Rapid, DNA-induced interface swapping by DNA gyrase

1. Thomas RM Germe
2. Natassja G Bush
3. Victoria M Baskerville
4. Dominik Saman
5. Justin LP Benesch
6. Anthony Maxwell

• Curated by eLife

  eLife assessment

  This is an important study on DNA gyrase that provides further evidence for its mode of action via a double-stranded DNA break and against a recently-proposed alternative mechanism. The evidence presented is solid and is derived from state-of-the-art techniques. The work casts new light on the interactions that occur between gyrase molecules and will be of interest to biochemists and cell biologists.

Reviewed by eLife

Semi‐synthetic nanobody‐ligand conjugates exhibit tunable signaling properties and enhanced transcriptional outputs at neurokinin receptor‐1

1. Nayara Braga Emidio
2. Ross W. Cheloha

Reviewed by Biophysics Colab

Structural dynamics of the active HER4 and HER2/HER4 complexes is finely tuned by different growth factors and glycosylation

1. Raphael Trenker
2. Devan Diwanji
3. Tanner Bingham
4. Kliment A Verba
5. Natalia Jura

• Curated by eLife

  eLife assessment

  This manuscript describes structures of HER4 homo- and HER4/HER2 hetero-dimer complexes using single particle cryo-EM. This important work describes convincingly new structural details of these complexes that expand our understanding of their function. This work will be of interest to researchers working on cell surface signalling and kinase activity.

Reviewed by eLife

Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane

1. Pragyansree Machhua
2. Vignesh Gopalakrishnan Unnithan
3. Yu Liu
4. Yiping Jiang
5. Lingfeng Zhang
6. Zhihong Guo

• Curated by eLife

  eLife assessment

  This valuable study describes the molecular mechanism of daptomycin insertion into bacterial membranes. The authors provide solid in vitro evidence for the early events of daptomycin interaction with phospholipid headgroups and stronger, specific interaction with phosphatidylglycerol. This work will be of interest to bacterial membrane biologists and biochemists working in the antimicrobial resistance field.

Reviewed by eLife

Guanidine production by plant homoarginine-6-hydroxylases

1. Dietmar Funck
2. Malte Sinn
3. Giuseppe Forlani
4. Jörg S Hartig

• Curated by eLife

  eLife assessment

  This fundamental study advances our understanding of nitrogen metabolism by identifying a new type of guanidine-forming enzyme in eukaryotes. The key claims of the article are convincingly supported by the data, with meticulous biochemical, cellular, and in vivo studies on guanidine production. The work will stimulate interest in the cellular roles of homoarginine, and, more generally, in the biochemistry and metabolism of guanidine derivatives.

Reviewed by eLife

Phosphorylation, disorder, and phase separation govern the behavior of Frequency in the fungal circadian clock

1. Daniyal Tariq
2. Nicole Maurici
3. Bradley M Bartholomai
4. Siddarth Chandrasekaran
5. Jay C Dunlap
6. Alaji Bah
7. Brian R Crane

• Curated by eLife

  eLife assessment

  This manuscript is a fundamental contribution to the understanding of the role of intrinsically disordered proteins in circadian clocks and the potential involvement of phase separation mechanisms. The authors convincingly report on the structural and biochemical aspects and the molecular interactions of the intrinsically disordered protein FRQ. The paper will be of interest to scientists focusing on circadian clock regulation, liquid-liquid phase separation, and phosphorylation.

Reviewed by eLife