Biochemistry

The cryo-EM structure of ASK1 reveals an asymmetric architecture allosterically modulated by TRX1

1. Karolina Honzejkova
2. Dalibor Kosek
3. Veronika Obsilova
4. Tomas Obsil

• Curated by eLife

  eLife assessment

  This important manuscript reports the cryo-EM structure of the ASK1 protein, which is a critical regulator of the MAPKs, JNKs, and p38 MAPKs in diverse cellular stress responses. The evidence of ASK1 interaction with TRX1 is compelling and will eventually allow the discovery of small molecule inhibitors of ASK1 activity.

Reviewed by eLife

Structure-guided mutagenesis of OSCAs reveals differential activation to mechanical stimuli

1. Sebastian Jojoa-Cruz
2. Adrienne E Dubin
3. Wen-Hsin Lee
4. Andrew B Ward

• Curated by eLife

  eLife assessment

  The manuscript seeks to dissect the molecular underpinnings of poke and stretch activation in OSCA channels. While the structural and functional experiments are well done, and the authors present some important data, the reviewers identified weaknesses in experimental design and interpretation that render the data incomplete in supporting some of the main conclusions of the paper. Nevertheless, this work will be of interest to those working in the fields of mechanosensation, sensory biology, and ion channels.

Reviewed by eLife

Structural mechanisms for VMAT2 inhibition by tetrabenazine

1. Michael P Dalton
2. Mary Hongying Cheng
3. Ivet Bahar
4. Jonathan A Coleman

• Curated by eLife

  eLife assessment

  The report presents the cryo-EM structure of human vesicular monoamine transporter 2 (VMAT2) bound to tetrabenazine, a clinical drug. VMAT2 is critical for neurotransmission, and the study constitutes an important milestone in neurotransmitter transport research. The evidence presented in the report is convincing and provides new opportunities for developing improved therapeutic interventions and furthering our understanding of this vital protein's function.

Reviewed by eLife

The non-muscle actinopathy-associated mutation E334Q in cytoskeletal γ-actin perturbs interaction of actin filaments with myosin and ADF/cofilin family proteins

1. Johannes N Greve
2. Anja Marquardt
3. Robin Heiringhoff
4. Theresia Reindl
5. Claudia Thiel
6. Nataliya Di Donato
7. Manuel H Taft
8. Dietmar J Manstein

• Curated by eLife

  eLife assessment

  This study presents a valuable characterization of the biochemical consequences of a disease-associated point mutation in a nonmuscle actin. The study uses well-characterized in vitro assays to explore function. The data are convincing and should be helpful to others.

Reviewed by eLife

DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks

1. Anja Göder
2. Chrystelle Antoinat Maric
3. Michael D. Rainey
4. Aisling O’Connor
5. Chiara Cazzaniga
6. Daniel Shamavu
7. Jean-Charles Cadoret
8. Corrado Santocanale

Reviewed by Review Commons

Structural basis of closed groove scrambling by a TMEM16 protein

1. Zhang Feng
2. Omar E. Alvarenga
3. Alessio Accardi

• Curated by Biophysics Colab

  Evaluation statement (17 January 2024; revised 31 January 2024)

  Feng and colleagues investigate the molecular basis of lipid scrambling in a fungal member of the TMEM16 family of Ca²⁺-dependent lipid scramblases. These proteins possess a groove in their 3D structure that has been implicated in lipid scrambling, which the authors investigate in the absence and presence of Ca²⁺ using a combination of cryo-EM structure determination, mutagenesis and functional assays. Their closed-groove structure reveals a continuous file of lipid molecules around the catalytic groove region, providing a structural basis for lipid interaction with the protein. Additionally, the authors capture three novel states of TMEM16, completing the picture of conformational transitions that this protein undergoes. Strikingly, the authors show that both structure and distribution of the protein’s conformations depend on lipid composition and nanodisc scaffold protein.

  Biophysics Colab considers this to be exceptional work and recommends it to scientists interested in plasma membrane lipid homeostasis and cryoEM.

  (This evaluation by Biophysics Colab refers to version 2 of this preprint, which has been revised in response to peer review of version 1.)

Reviewed by Biophysics Colab

Remote loop evolution reveals a complex biological function for chitinase enzymes beyond the active site

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

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