Biochemistry

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

Branched‐chain amino acid synthesis is coupled to TOR activation early in the cell cycle in yeast

1. Heidi M Blank
2. Carsten Reuse
3. Kerstin Schmidt‐Hohagen
4. Staci E Hammer
5. Karsten Hiller
6. Michael Polymenis

Reviewed by Review Commons

Ancestral protein reconstruction reveals evolutionary events governing variation in Dicer helicase function

1. Adedeji M Aderounmu
2. P Joseph Aruscavage
3. Bryan Kolaczkowski
4. Brenda L Bass

• Curated by eLife

  eLife assessment

  This is a valuable paper describing an attempt to reconstruct the evolution of Dicer. Using ancestral reconstruction approaches, the authors carefully examine the biochemical characteristics of reconstructed proteins at various junction points in the animal lineage. They provide solid evidence that the deepest ancestrally reconstructed protein has double-stranded RNA stimulated ATPase activity and that this characteristic was lost along the vertebrate lineage. This paper will be of interest to scientists in the RNA-protein interaction and protein evolution fields.

Reviewed by eLife

Aedes aegypti eggs use rewired polyamine and lipid metabolism to survive extreme desiccation

1. Anjana Prasad
2. Sreesa Sreedharan
3. Baskar Bakthavachalu
4. Sunil Laxman

Reviewed by Review Commons

Optical tools for visualizing and controlling human GLP-1 receptor activation with high spatiotemporal resolution

1. Loïc Duffet
2. Elyse T Williams
3. Andrea Gresch
4. Simin Chen
5. Musadiq A Bhat
6. Dietmar Benke
7. Nina Hartrampf
8. Tommaso Patriarchi

• Curated by eLife

  eLife assessment

  This valuable Tools and Resources paper presents new tools for investigating GLP-1 signaling: a genetically-encoded sensor constructed from a mutated GLP1R receptor as well as a caged agonist peptide. The evidence for these tools working as advertised is solid and they may be helpful for screening compounds that bind to GLP1R.

Reviewed by eLife

Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii

1. Amit Kumar
2. Oscar Vadas
3. Nicolas Dos Santos Pacheco
4. Xu Zhang
5. Kin Chao
6. Nicolas Darvill
7. Helena Ø Rasmussen
8. Yingqi Xu
9. Gloria Meng-Hsuan Lin
10. Fisentzos A Stylianou
11. Jan Skov Pedersen
12. Sarah L Rouse
13. Marc L Morgan
14. Dominique Soldati-Favre
15. Stephen Matthews

• Curated by eLife

  eLife assessment

  The authors describe the first full-length crystal structure and solution conformation of the GAC protein from Toxoplasma gondii. The data are convincing and support a model in which GAC uses multiple conformations and lipid-binding surfaces. This paper presents an important contribution to our understanding of the molecular machinery involved in host cell invasion, but questions remain about how this protein links to the cytoskeleton and functions during the invasion process.

Reviewed by eLife

Cryo-EM structure of the endothelin-1-ETB-Gi complex

1. Fumiya K Sano
2. Hiroaki Akasaka
3. Wataru Shihoya
4. Osamu Nureki

• Curated by eLife

  eLife assessment

  Based on the Cryo-EM structure of human ETB in complex with the vasoconstricting peptide ET-1 and the inhibitory G-protein (Gi), this valuable study presents convincing data on how agonist binding is coupled to Gi-protein binding. The complex structure is solid and will appeal to the GPCR and pharmacology communities.

Reviewed by eLife

Concurrent remodelling of nucleolar 60S subunit precursors by the Rea1 ATPase and Spb4 RNA helicase

1. Valentin Mitterer
2. Matthias Thoms
3. Robert Buschauer
4. Otto Berninghausen
5. Ed Hurt
6. Roland Beckmann

• Curated by eLife

  eLife assessment

  This fundamental study substantially advances our understanding of the process of ribosome maturation. The authors have purified and determined the structures of several nucleolar ribosome assembly intermediates in yeast using cryo-electron microscopy (cryo-EM). The study combines genetic, biochemical, and structural analysis to provide compelling support for the conclusions the authors wish to draw. The work will be of broad interest to cell biologists, biochemists, and structural biologists.

Reviewed by eLife