Biochemistry

Vibrio cholerae’s ToxRS bile sensing system

1. Nina Gubensäk
2. Theo Sagmeister
3. Christoph Buhlheller
4. Bruno Di Geronimo
5. Gabriel E Wagner
6. Lukas Petrowitsch
7. Melissa A Gräwert
8. Markus Rotzinger
9. Tamara M Ismael Berger
10. Jan Schäfer
11. Isabel Usón
12. Joachim Reidl
13. Pedro A Sánchez-Murcia
14. Klaus Zangger
15. Tea Pavkov-Keller

• Curated by eLife

  eLife assessment

  This study provides important insights into the structural biology and molecular mechanism of the sensory proteins ToxR/S that are associated with survival and virulence of the cholera pathogen. The structural studies are solid and supported by a series of biophysical experiments revealing a split, periplasmic protein binding interface for bile acid. The results are of interest to both protein biochemistry and pharmacology, potentially opening new routes for intervention in cholera disease.

Reviewed by eLife

Indole produced during dysbiosis mediates host–microorganism chemical communication

1. Rui-Qiu Yang
2. Yong-Hong Chen
3. Qin-yi Wu
4. Jie Tang
5. Shan-Zhuang Niu
6. Qiu Zhao
7. Yi-Cheng Ma
8. Cheng-Gang Zou

• Curated by eLife

  eLife assessment

  This fundamental study provides compelling evidence for a new mechanism of host-microbe interaction, with indole, produced by proliferating bacteria in the C. elegans digestive system, signalling through the host via the transcription factor DAF-16 to induce the expression of genes controlling bacterial growth in the gut. The work is relevant to a wide audience as it invites deeper research into this mechanism, while also serving as a template for similar microbiome/host interactions in other systems.

Reviewed by eLife

Mechanism of substrate binding and transport in BASS transporters

1. Patrick Becker
2. Fiona Naughton
3. Deborah Brotherton
4. Raul Pacheco-Gomez
5. Oliver Beckstein
6. Alexander D Cameron

• Curated by eLife

  eLife assessment

  The manuscript represents an important contribution to an ongoing discussion about the substrate binding site and mechanism of the Bile Acid Sodium Symporter (BASS) family of transporters. Structural and biochemical analysis of a bacterial homolog, ASTBnm, in complex with its native substrate (not bile acids, but a vitamin A precursor, pantoate) show a new binding site that is consistent with classical proposals for elevator-type transport mechanisms. Molecular dynamics (MD) simulations highlight the improved stability for the substrate in the active site when ions are present, suggesting a binding order during the transport cycle. The structural studies, binding assays, and MD simulations are convincing.

Reviewed by eLife

The neuronal calcium sensor NCS-1 regulates the phosphorylation state and activity of the Gα chaperone and GEF Ric-8A

1. Daniel Muñoz-Reyes
2. Levi J McClelland
3. Sandra Arroyo-Urea
4. Sonia Sánchez-Yepes
5. Juan Sabín
6. Sara Pérez-Suárez
7. Margarita Menendez
8. Alicia Mansilla
9. Javier García-Nafría
10. Stephen Sprang
11. Maria Jose Sanchez-Barrena

• Curated by eLife

  eLife assessment

  This important study reports biochemical and structural experiments that were carried out to determine the molecular basis of calcium-sensitive regulation of the guanine exchange factor Ric8A by the neuronal calcium sensor 1 (NCS-1). Structural and biochemical evidence for the NCS-1/Ric8A interface is convincing, but evidence for the full-length interactions is incomplete due to the low resolution of cryo-EM maps. This work will have important implications for scientists interested in G-protein signaling and molecular interactions that contribute to synapse function.

Reviewed by eLife

Structural rather than catalytic role for mitochondrial respiratory chain supercomplexes

1. Michele Brischigliaro
2. Alfredo Cabrera-Orefice
3. Susanne Arnold
4. Carlo Viscomi
5. Massimo Zeviani
6. Erika Fernández-Vizarra

• Curated by eLife

  eLife assessment

  This study presents valuable findings on the organization of respiratory chain complexes in mitochondria. It provides solid evidence that respiratory supercomplex formation in the fruit fly does not impact respiratory function, suggesting the role of these complexes is structural, rather than catalytic. However, whether the conclusions extend to other species requires further evidence. This manuscript will be of broad interest to the field of mitochondrial bioenergetics.

Reviewed by eLife

An unconventional gatekeeper mutation sensitizes inositol hexakisphosphate kinases to an allosteric inhibitor

1. Tim Aguirre
2. Gillian L Dornan
3. Sarah Hostachy
4. Martin Neuenschwander
5. Carola Seyffarth
6. Volker Haucke
7. Anja Schütz
8. Jens Peter von Kries
9. Dorothea Fiedler

• Curated by eLife

  eLife assessment

  This manuscript describes a fundamental strategy for developing isozyme-selective inhibitors of inositol hexakisphosphate kinases. The compelling evidence that subtle changes to the gatekeeper position can sensitize the inositol hexakisphosphate kinase mutant to allosteric inhibitors will undoubtedly inspire other analog-sensitive inhibitor studies. This manuscript will be of interest to researchers focusing on kinase regulation and inhibitor design.

Reviewed by eLife

Oligomerization-dependent and synergistic regulation of Cdc42 GTPase cycling by a GEF and a GAP

1. Sophie Tschirpke
2. Werner K-G. Daalman
3. Frank van Opstal
4. Liedewij Laan

Reviewed by Review Commons

MEMO1 binds iron and modulates iron homeostasis in cancer cells

1. Natalia Dolgova
2. Eva-Maria E Uhlemann
3. Michal T Boniecki
4. Frederick S Vizeacoumar
5. Anjuman Ara
6. Paria Nouri
7. Martina Ralle
8. Marco Tonelli
9. Syed A Abbas
10. Jaala Patry
11. Hussain Elhasasna
12. Andrew Freywald
13. Franco J Vizeacoumar
14. Oleg Y Dmitriev

• Curated by eLife

  eLife assessment

  Dolgova et al present a well-written and important manuscript focused on the mechanism of MEMO1 function in tumor cells. The authors explore whether the mechanism of MEMO1 overexpression in breast cancer, especially TNBC, is related to regulating iron given evidence that MEMO1 binds multiple proteins in the iron regulation pathway. While the data is in part compelling, the claims are based on indirect evidence for a central role of MEMO1 in tumorogenesis and perhaps metastasis via its effect on iron homeostasis.

Reviewed by eLife

Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stress

1. Jinyang Wang
2. Yaxin Wen
3. Wentao Zhao
4. Yan Zhang
5. Furong Lin
6. Cong Ouyang
7. Huihui Wang
8. Lizheng Yao
9. Huanhuan Ma
10. Yue Zhuo
11. Huiying Huang
12. Xiulin Shi
13. Liubin Feng
14. Donghai Lin
15. Bin Jiang
16. Qinxi Li

• Curated by eLife

  eLife assessment

  This is important work that examines hepatic acetate production via ACOT12/18 in starvation and diabetes. The investigators use solid loss of function strategies in cells, including mouse primary hepatocytes, and in vivo mouse experiments to show that ACOTs are necessary for normal acetate production in the context of fasting and type 1 diabetes. Given that acetate is commonly thought to primarily represent a fermentation product, this study is of interest as it describes hepatic pathways converting fatty acids to acetate.

Reviewed by eLife

Structural basis for the phase separation of the chromosome passenger complex

1. Nikaela W Bryan
2. Aamir Ali
3. Ewa Niedzialkowska
4. Leland Mayne
5. P Todd Stukenberg
6. Ben E Black

Reviewed by Review Commons