Biochemistry

Utilizing a nanobody recruitment approach for assessing serine palmitoyltransferase activity in ER sub-compartments of yeast

1. Bianca M. Esch
2. Stefan Walter
3. Oliver Schmidt
4. Florian Fröhlich

Reviewed by Review Commons

Structure of the connexin-43 gap junction channel in a putative closed state

1. Chao Qi
2. Silvia Acosta Gutierrez
3. Pia Lavriha
4. Alaa Othman
5. Diego Lopez-Pigozzi
6. Erva Bayraktar
7. Dina Schuster
8. Paola Picotti
9. Nicola Zamboni
10. Mario Bortolozzi
11. Francesco Luigi Gervasio
12. Volodymyr M Korkhov

• Curated by eLife

  eLife assessment

  Gap junctions, formed from connexins, are important in cell communication, allowing ions and small molecules to move directly between cells. By determining the Cryo EM structure of the structure of connexin 43 in a putative closed state involving lipids, the study makes an important contribution to the development of a mechanistic model for connexin activation. The connexin 43 structure is solid and its presentation will appeal to the channel and membrane protein communities.

Reviewed by eLife

Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain

1. Noah J Harris
2. Meredith L Jenkins
3. Sung-Eun Nam
4. Manoj K Rathinaswamy
5. Matthew AH Parson
6. Harish Ranga-Prasad
7. Udit Dalwadi
8. Brandon E Moeller
9. Eleanor Sheeky
10. Scott D Hansen
11. Calvin K Yip
12. John E Burke

• Curated by eLife

  eLife assessment

  This study presents fundamental new insight into the regulatory apparatus of PI3Kγ, a kinase in signaling pathways that control the immune response and cancer. A suite of biophysical and biochemical approaches provide convincing evidence for new sites of allosteric control over enzyme activity. The rigorous findings provide structure and dynamic information that may be exploited in efforts to control PI3Kγ activity in a therapeutic setting.

Reviewed by eLife

A novel single alpha-helix DNA-binding domain in CAF-1 promotes gene silencing and DNA damage survival through tetrasome-length DNA selectivity and spacer function

1. Ruben Rosas
2. Rhiannon R Aguilar
3. Nina Arslanovic
4. Anna Seck
5. Duncan J Smith
6. Jessica K Tyler
7. Mair EA Churchill

• Curated by eLife

  eLife assessment

  The important paper describes the structure of a single alpha helix in the large subunit of the Chromatin Assembly Factor 1 (CAF-1) that binds DNA. The single alpha-helix DNA interaction is novel and, combined with the CAF-1 Winged Helix Domain, is required for CAF-1 function in vivo for gene silencing and DNA damage response. The data are convincing, but there are additional analyses that may be considered.

Reviewed by eLife

Proteostasis is differentially modulated by inhibition of translation initiation or elongation

1. Khalyd J Clay
2. Yongzhi Yang
3. Christina Clark
4. Michael Petrascheck

• Curated by eLife

  eLife assessment

  This manuscript is of interest for the fields of ageing, mRNA translation and C. elegans biology, as it provides new insights into the regulation of lifespan by alternate mechanisms that modulate mRNA translation in selected environmental contexts. While overall the main conclusions are supported by the data and of interest, the work would be stronger with control experiments that more fully and more consistently support all the conclusions. Furthermore, data presentation and interpretation need some attention.

Reviewed by eLife

The ER folding sensor UGGT1 acts on TAPBPR-chaperoned peptide-free MHC I

1. Lina Sagert
2. Christian Winter
3. Ina Ruppert
4. Maximilian Zehetmaier
5. Christoph Thomas
6. Robert Tampé

• Curated by eLife

  eLife assessment

  This valuable study reports a complete in vitro system where different steps and direct interactions between different components of MHCI maturation can be monitored, hence leading to a better mechanistic understanding of MHC I maturation. The evidence supporting the findings is currently incomplete and would benefit from clarification of some key issues. This work will be of interest to immunologists and biochemists.

Reviewed by eLife

Distant sequence regions of JBP1 contribute to J-DNA binding

1. Ida de Vries
2. Danique Ammerlaan
3. Tatjana Heidebrecht
4. Patrick HN Celie
5. Daan P Geerke
6. Robbie P Joosten
7. Anastassis Perrakis

Reviewed by Review Commons

Structural insight into guanylyl cyclase receptor hijacking of the kinase–Hsp90 regulatory mechanism

1. Nathanael A Caveney
2. Naotaka Tsutsumi
3. K Christopher Garcia

• Curated by eLife

  eLife assessment

  In this important study, the human membrane receptor guanyl cyclase GC-C was expressed in hamster cells, co-purified in complex with endogenous HSP90 and CDC37 proteins, and the structure of the complex was determined by cryo-EM. The study shows that the pseudo-kinase domain of GC-C associates with CDC37 and HSP90, similarly to how the bona fide protein kinases CDK4, CRAF and BRAF have been shown to interact. The methodology used is state of the art and the evidence presented is compelling.

Reviewed by eLife

Molecular basis of ligand-dependent Nurr1-RXRα activation

1. Xiaoyu Yu
2. Jinsai Shang
3. Douglas J Kojetin

• Curated by eLife

  eLife assessment

  This is a fundamental study of the activation process of Nurr1, an orphan nuclear receptor that may be a significant target for the treatment of neurodegenerative disorders. Nurr1 functions as a monomer, but may also heterodimerize with RXR which represses Nurr1 transcriptional activation. The authors provide compelling evidence for Nurr1 activation through ligand-induced dissociation of an inactive Nurr1-RXRa heterodimer. These data will be important for biochemists and cell biologists working on regulatory / activation mechanisms of nuclear hormone receptors.

Reviewed by eLife

Phase separation-mediated actin bundling by the postsynaptic density condensates

1. Xudong Chen
2. Bowen Jia
3. Shihan Zhu
4. Mingjie Zhang

• Curated by eLife

  eLife assessment

  This manuscript presents an exciting set of experiments on the mechanisms through which PSD proteins induce actin bundle formation. The work included deep mechanistic analyses which determine the necessity of upper vs. lower levels of PSD proteins for actin bundle formation, identify the domains and interactions of these proteins that are necessary and sufficient to induce actin bundles, and provide a first assessment in neurons of potential roles of the newly discovered mechanisms.

Reviewed by eLife