Biochemistry

Mechanistic Studies of Small Molecule Ligands Selective to RNA Single G Bulges

1. Shalakha Hegde
2. Sana Akhter
3. Zhichao Tang
4. Chang Qi
5. Chenguang Yu
6. Anna Lewicka
7. Yu Liu
8. Kushal Koirala
9. Mikhail Reibarkh
10. Kevin P. Battaile
11. Anne Cooper
12. Scott Lovell
13. Erik D. Holmstrom
14. Xiao Wang
15. Joseph A. Piccirilli
16. Qi Gao
17. Yinglong Miao
18. Jingxin Wang

Reviewed by PREreview

The co-receptor Tetraspanin12 directly captures Norrin to promote ligand-specific β-catenin signaling

1. Elise S Bruguera
2. Jacob P Mahoney
3. William I Weis

• Curated by eLife

  eLife Assessment

  This is a fundamental study that addresses the key question of how the tetraspanin Tspan12 functions biochemically as a co-receptor for Norrin to initiate β-catenin signaling. The strength of the work lies in the rigorous and compelling binding analyses involving various purified receptors, co-receptors, and ligands, as well as molecular modeling by AlphaFold that was subsequently validated by an extensive series of mutagenesis experiments. The study advances the field by providing a novel mechanism of co-receptor function and shedding new light on how signaling specificity is achieved in the complex Wnt/Norrin signaling system.

Reviewed by eLife

Structure of the human CTF18 clamp loader bound to PCNA

1. Giuseppina R Briola
2. Muhammad Tehseen
3. Amani Al-Amodi
4. Phong Quoc Nguyen
5. Christos G Savva
6. Samir M Hamdan
7. Alfredo De Biasio

• Curated by eLife

  eLife Assessment

  Briola and co-authors determined the structure of the human CTF18 clamp loader bound to PCNA to high resolution, analyzed the structure, and tested a new mechanism involving a human-specific Ctf18 beta-hairpin docking onto Rfc5, which represents a valuable contribution. The data are solid and complement data recently published by others.

Reviewed by eLife

Protonation/deprotonation-driven switch for the redox stability of low-potential [4Fe-4S] ferredoxin

1. Kei Wada
2. Kenji Kobayashi
3. Iori Era
4. Yusuke Isobe
5. Taigo Kamimura
6. Masaki Marukawa
7. Takayuki Nagae
8. Kazuki Honjo
9. Noriko Kaseda
10. Yumiko Motoyama
11. Kengo Inoue
12. Masakazu Sugishima
13. Katsuhiro Kusaka
14. Naomine Yano
15. Keiichi Fukuyama
16. Masaki Mishima
17. Yasutaka Kitagawa
18. Masaki Unno

• Curated by eLife

  eLife Assessment

  Ferredoxins are ubiquitous electron transfer proteins that drive essential metabolic processes across all domains of life. This fundamental contribution to the field provides the first description of how specific amino acids, though a series of hydrogen bonds, control the ability of iron-sulfur clusters in ferrodoxins to accept and donate electrons. The evidence supporting the conclusions is compelling as is the combined use of neutron crystallography with X-ray crystallography and classical spectral/redox studies.

Reviewed by eLife

Interactions with multiple inner kinetochore proteins determine mitotic localization of FACT

1. Julia Schweighofer
2. Bhagyashree Mulay
3. Ingrid Hoffmann
4. Doro Vogt
5. Marion E. Pesenti
6. Andrea Musacchio

Reviewed by Review Commons

Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane

1. Pragyansree Machhua
2. Vignesh Gopalakrishnan Unnithan
3. Yu Liu
4. Yiping Jiang
5. Lingfeng Zhang
6. Zhihong Guo

• Curated by eLife

  eLife Assessment

  This valuable study describes the molecular mechanism of daptomycin insertion into bacterial membranes. The authors provide solid in vitro evidence for the early events of daptomycin interaction with phospholipid headgroups and stronger, specific interaction with phosphatidylglycerol. This work will be of interest to bacterial membrane biologists and biochemists working in the antimicrobial resistance field.

Reviewed by eLife

Seeing Double: Molecular dynamics simulations reveal the stability of certain alternate protein conformations in crystal structures

1. Aviv A. Rosenberg
2. Sanketh Vedula
3. Alex M. Bronstein
4. Ailie Marx

Reviewed by PREreview

Determining the off-target activity of antibiotics and novel translation initiation sites in mitochondria

1. James Marks
2. Emma Young
3. Markus Hafner

• Curated by eLife

  eLife Assessment

  This useful study presents findings on how some antibiotics, which inhibit protein synthesis in bacteria, affect the translation in mitochondrial ribosomes. The authors provide solid evidence that most tested antibiotics act similarly on bacterial and mitochondrial translation. Additionally, this work shows that alternative translation initiation events might exist in two specific mt-mRNAs (MT-ND1 and MT-ND5). The conclusions of this manuscript are of broad interest to the antibiotic and the mitochondrial fields.

Reviewed by eLife

Increased bone inflammation in type 2 diabetes and obesity correlates with Wnt signaling downregulation and reduced bone strength

1. Giulia Leanza
2. Malak Faraj
3. Francesca Cannata
4. Viola Viola
5. Niccolò Pellegrini
6. Flavia Tramontana
7. Claudio Pedone
8. Gianluca Vadalà
9. Alessandra Piccoli
10. Rocky Strollo
11. Francesca Zalfa
12. Roberto Civitelli
13. Mauro Maccarrone
14. Rocco Papalia
15. Nicola Napoli

• Curated by eLife

  eLife Assessment

  This is a convincing paper that addresses topics important in our understanding of how inflammatory markers are modulated in both obesity and type 2 diabetes and their effects on Wnt signaling mediators in human bone. There are changes in bone at the tissue level in these 2 common metabolic disorders that ultimately lead to compromised bone strength. These data will be critical to our understanding of the pathophysiology of skeletal fragility in obesity and diabetes.

Reviewed by eLife

Control of 3′ splice site selection by the yeast splicing factor Fyv6

1. Katherine A Senn
2. Karli A Lipinski
3. Natalie J Zeps
4. Amory F Griffin
5. Max E Wilkinson
6. Aaron A Hoskins

• Curated by eLife

  eLife Assessment

  This important study addresses how 3' splice site choice is modulated by the conserved spliceosome-associated protein Fyv6. The authors provide compelling evidence that Fyv6 functions to enable selection of 3' splice sites distal to a branch point and in doing so antagonizes more proximal, suboptimal 3' splice sites.

Reviewed by eLife