Biochemistry

The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase

1. Valentin Bohl
2. Nele Merret Hollmann
3. Tobias Melzer
4. Panagiotis Katikaridis
5. Lena Meins
6. Bernd Simon
7. Dirk Flemming
8. Irmgard Sinning
9. Janosch Hennig
10. Axel Mogk

• Curated by eLife

  eLife assessment

  This important manuscript details the characterization of ClpL from L. monocytogenes as an effective and autonomous AAA+ disaggregase that provides enhanced heat resistance to this food-borne pathogen. Supported by compelling evidence, the authors demonstrate that ClpL has DnaK-independent disaggregase activity towards a variety of aggregated model substrates, which is more potent than that observed with the endogenous canonical DnaK/ClpB bi-chaperone system. The work will be of broad interest to microbiologists and biochemists.

Reviewed by eLife

Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia

1. Raji E. Joseph
2. Thomas E. Wales
3. Sandrine Jayne
4. Robert G. Britton
5. D. Bruce Fulton
6. John R. Engen
7. Martin J. S. Dyer
8. Amy H. Andreotti

• Curated by eLife

  eLife assessment

  The manuscript reports on an important comparison of a range of approved clinical inhibitors for BTK used for the treatment of chronic lymphocytic leukemia (CLL). The authors provide solid evidence for their claims, using a combination of HDX-MS and NMR spectroscopy. The novelty is that this study also seeks to evaluate resistance mutation bias. The scope of the study is highly exciting but would benefit from a clear link of the biophysical studies to the functional assays - specifically nucleotide binding.

Reviewed by eLife

X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX

1. Isabelle Petit-Hartlein
2. Annelise Vermot
3. Michel Thepaut
4. Anne-Sophie Humm
5. Florine Dupeux
6. Jerome Dupuy
7. Vincent Chaptal
8. Jose Antonio Marquez
9. Susan ME Smith
10. Franck Fieschi

• Curated by eLife

  eLife assessment

  In this manuscript, the authors investigate the properties of prokaryotic NADPH oxidases (NOX) and discuss the implications for NOX regulation and function. The structure of the S. pneumoniae Nox protein is an important step forward in our understanding of procaryotic NOX enzymes and the characterization and interpretation are convincing. The results will be of interest to structural biologists as well as biochemists focusing on enzymatic functions.

Reviewed by eLife

The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body

1. Alexander Stadler
2. Laryssa De Liz
3. Heloisa B. Gabriel
4. Santiago Alonso-Gil
5. Robbie Crickley
6. Katharina Korbula
7. Bojan Žagrović
8. Sue Vaughan
9. Jack D. Sunter
10. Gang Dong

Reviewed by Review Commons

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 Maric
3. Michael D. Rainey
4. Chiara Cazzaniga
5. Daniel Shamavu
6. Jean-Charles Cadoret
7. 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