Biochemistry

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

Recognition and cleavage of human tRNA methyltransferase TRMT1 by the SARS-CoV-2 main protease

1. Angel D'Oliviera
2. Xuhang Dai
3. Saba Mottaghinia
4. Sophie Olson
5. Evan P Geissler
6. Lucie Etienne
7. Yingkai Zhang
8. Jeffrey S Mugridge

• Curated by eLife

  eLife Assessment

  This manuscript provides important structural insights into the recognition and degradation of the host tRNA methyltransferase TRMT1 by SARS-CoV-2 protease nsp5 (Mpro). The data provide compelling support for the main conclusions of the authors. These results will be of interest to researchers studying structures, substrate recognition and specificity of viral proteases and their action on cellular targets.

Reviewed by eLife

The chromokinesin Kid (KIF22) forms a homodimer, moves processively along microtubules and transports double-strand DNA

1. Shinsuke Niwa
2. Natsuki Furusaki
3. Tomoki Kita
4. Yuki Suzuki
5. Kyoko Chiba

• Curated by eLife

  eLife Assessment

  This valuable study clarifies the mechanism by which the kinesin-10 motor protein, chromosome-associated kinesin, Kid (KIF22), enables chromosome movement during mitosis, demonstrating that human and Xenopus Kid proteins function as processive, homodimeric kinesins capable of processive microtubule plus-end motility. The convincing work highlights that Kid can recruit and transport duplex DNA along microtubules via its conserved C-terminal DNA binding domain, revising our understanding of chromokinesins' role in chromosome motility during mitosis. Although the data are robust, the manuscript would benefit from some editing for clarity.

Reviewed by eLife

Identification of suitable target/E3 ligase pairs for PROTAC development using a rapamycin-induced proximity assay (RiPA)

1. Bikash Adhikari
2. Katharina Schneider
3. Mathias Diebold
4. Christoph Sotriffer
5. Elmar Wolf

• Curated by eLife

  eLife Assessment

  The study describes a valuable new technology in the field of targeted protein degradation that allows identification of E3-ubiquitin ligases that target a protein of interest. The presented data are convincing, however, additional work will be needed to optimize for high-throughput evaluation. This technology will therefore serve the community in the initial stages of developing targeted protein degraders.

Reviewed by eLife

Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50

1. Eyal Paz
2. Sahil Jain
3. Irit Gottfried
4. Orna Staretz-Chacham
5. Muhammad Mahajnah
6. Pritha Bagchi
7. Nicholas T Seyfried
8. Uri Ashery
9. Abdussalam Azem

• Curated by eLife

  eLife Assessment

  This important study presents interesting results aimed at explaining the effects of a human mutation on the mitochondrial import protein TIMM50 on mitochondrial function and neuronal excitability. While the evidence supporting the conclusions is convincing, the mechanisms driving changes in the levels of certain proteins within and outside the mitochondria (such as certain ion channels) remain unexplained. This paper will be of interest to scientists in the mitochondria field.

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 JS 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 compelling 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 manuscript will be of high interest to scientists working on protein drug interactions.

Reviewed by eLife

Biochemical and structural insights into the auto-inhibited state of Mical1 and its activation by Rab8

1. Amrita Rai
2. Petra Janning
3. Ingrid R Vetter
4. Roger S Goody

• Curated by eLife

  eLife Assessment

  This fundamental study addresses the regulation of the MICAL-family of actin regulators by Rab GTPases, which play a key role in directing membrane trafficking within cells. The compelling evidence explains how Rab8 family members bind at two sites to allosterically regulate MICAL1, and relieve an auto-inhibited state unable to bind actin. This study lays the basis for further progress in understanding membrane trafficking and cytoskeleton dynamics in eukaryotic cells.

Reviewed by eLife