Biochemistry

Discovery of a new class of reversible TEA domain transcription factor inhibitors with a novel binding mode

1. Lu Hu
2. Yang Sun
3. Shun Liu
4. Hannah Erb
5. Alka Singh
6. Junhao Mao
7. Xuelian Luo
8. Xu Wu

• Curated by eLife

  Evaluation Summary:

  Hu and colleagues describe the discovery and characterization of a new class of reversible palmitoylation (PLM) binding site TEAD inhibitors. X-ray co-crystallographic analysis reveals that the ligand class, identified from a screen of 30,000 small molecules, binds to a new site within the auto-PLM site. The TM2 lead compound inhibits the growth of NF2-deficient cell lines. The discovery has the potential to significantly impact the design and development of new effective TEAD inhibitors. Some clarification or additional data are required to support and justify some of the authors' claims regarding the molecular significance of this new class of inhibitors.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Human mtRF1 terminates COX1 translation and its ablation induces mitochondrial ribosome-associated quality control

1. Franziska Nadler
2. Elena Lavdovskaia
3. Angelique Krempler
4. Luis Daniel Cruz-Zaragoza
5. Sven Dennerlein
6. Ricarda Richter-Dennerlein

Reviewed by ASAPbio crowd review

Distinct architectural requirements for the parS centromeric sequence of the pSM19035 plasmid partition machinery

1. Andrea Volante
2. Juan Carlos Alonso
3. Kiyoshi Mizuuchi

• Curated by eLife

  Evaluation Summary:

  The work by Volante et al. studied a new plasmid partition system, in which the authors discovered that four or more contiguous ParS sequence repeats are required to assemble a stable partitioning ParAB complex and to activate the ParA ATPase. The work reveals a new plasmid partitioning mechanism in which the mechanic property of DNA and its interaction with the partition complex may drive the directional movement of the plasmid.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Structural mechanism of CRL4‐instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor

1. Vu Thuy Khanh Le‐Trilling
2. Sofia Banchenko
3. Darius Paydar
4. Pia Madeleine Leipe
5. Lukas Binting
6. Simon Lauer
7. Andrea Graziadei
8. Robin Klingen
9. Christine Gotthold
10. Jörg Bürger
11. Thilo Bracht
12. Barbara Sitek
13. Robert Jan Lebbink
14. Anna Malyshkina
15. Thorsten Mielke
16. Juri Rappsilber
17. Christian MT Spahn
18. Sebastian Voigt
19. Mirko Trilling
20. David Schwefel

Reviewed by Review Commons

Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter

1. Martin F. Peter
2. Jan A. Ruland
3. Peer Depping
4. Niels Schneberger
5. Emmanuele Severi
6. Jonas Moecking
7. Karl Gatterdam
8. Sarah Tindall
9. Alexandre Durand
10. Veronika Heinz
11. Jan Peter Siebrasse
12. Paul-Albert Koenig
13. Matthias Geyer
14. Christine Ziegler
15. Ulrich Kubitscheck
16. Gavin H. Thomas
17. Gregor Hagelueken

• Curated by Biophysics Colab

  Endorsement statement (5 August 2022)

  Peter et al. describe the first experimentally validated structural model of a canonical member of the TRAP family of transporters, Haemophilus influenzae (Hi)SiaPQM, which transports sialic acid into bacteria. By elegantly combining a cryo-EM structure of the HiSiaQM dimer, AlphaFoldmodels, and sequence, biochemical, and mutational analyses, the authors shed light on the fold and domain organization of the tripartite HiSiaPQM holocomplex. The authors also propose a structure-based model for its transport mechanism: substrate recognition is "outsourced" to the substrate binding protein (P protein) by the QM proteins, which in turn use an elevator mechanism to transport sialic acid across the membrane. The work is rigorous and convincing, and it presents valuable findings that will be of interest to scientists investigating transporters with an elevator-type mechanism as well as membrane transport more generally.

  (This endorsement by Biophysics Colab refers to the version of record for this work, which is linked to and has been revised from the original preprint following peer review.)

Reviewed by Biophysics Colab

Structural basis for RNA-mediated assembly of type V CRISPR-associated transposons

1. Michael Schmitz
2. Irma Querques
3. Seraina Oberli
4. Christelle Chanez
5. Martin Jinek

Reviewed by ASAPbio crowd review

Multi-step recognition of potential 5' splice sites by the Saccharomyces cerevisiae U1 snRNP

1. Sarah R Hansen
2. David S White
3. Mark Scalf
4. Ivan R Corrêa
5. Lloyd M Smith
6. Aaron A Hoskins

• Curated by eLife

  Evaluation Summary:

  This study extends previous work from the same group on the mechanism of 5' splice site recognition using co-localization single-molecule spectroscopy. There are three important conclusions: 1) the association of the U1 snRNP with the 5' splice site is largely determined by the snRNP itself and does not require other splicing factors; 2) sequence features of the 5' splice site determine whether a short-lived complex with U1 dissociates or transitions into a longer-lived, "productive" complex, potentially mediated by stabilized contacts with U1 associated proteins; and 3) the ability to form the longer-lived complex cannot be accurately predicted by base-pairing potential alone, as presumed by many predictive algorithms. Currently, a test for the role of specific protein-RNA contacts is lacking; additionally, a comparison with other nucleic acid recognition events is missing, particularly those also showing a two-step binding mechanism. This work will be of interest to colleagues in the splicing field as well as to others in fields where nucleic acid recognition by snRNPs plays a major role.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein

1. Matthew Ravalin
2. Heegwang Roh
3. Rahul Suryawanshi
4. G. Renuka Kumar
5. John E. Pak
6. Melanie Ott
7. Alice Y. Ting

Reviewed by ASAPbio crowd review

Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition

1. Yitong Li
2. Vijaya Kumar Balakrishnan
3. Michael Rowse
4. Cheng-Guo Wu
5. Anastasia Phoebe Bravos
6. Vikash K Yadav
7. Ylva Ivarsson
8. Stefan Strack
9. Irina V Novikova
10. Yongna Xing

• Curated by eLife

  Evaluation Summary:

  Xing and colleagues present a cryoEM structure of the protein phosphatase 2A (PP2A)-B56 holoenzyme in complex with protein phosphatase methyltransferase-1 (PME-1). The structure reveals that PME-1 blocks the substrate binding site of PP2A by inserting an unstructured loop. This unexpected inhibitory mechanism is also coupled to a large conformation change in the PP2A-B56 holoenzyme and PME-1. Combined with biochemical and cellular assays, the authors suggest how PME-1 can regulate p53-mediated DNA damage responses via inhibiting PP2A. This manuscript will be of importance for structural biologists as well as colleagues in the p53 field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Membrane-mediated dimerization potentiates PIP5K lipid kinase activity

1. Scott D Hansen
2. Albert A Lee
3. Benjamin R Duewell
4. Jay T Groves

• Curated by eLife

  Evaluation Summary:

  This paper is of interest for a wide range of readers who study the biology of lipid modifying enzymes, especially as it relates to interfacial reaction kinetics in biological membranes. This study aimed to obtain detailed biochemical insights into the mutual relationship between PI(4,5)P2 lipids and their kinase PIP5K, which engage in an exciting pattern-forming reaction on membranes. The authors find cooperative recruitment of PIP5K to the membrane, oligomerization-enhanced catalytic efficiency and indications of allosteric regulation. Although of very high interest and featuring mostly convincing data, there are concerns about the interpretation of whether the observed phenomenon is dimer specific or related to higher-order oligomerization. In addition, there are inconsistencies in the data presentation.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife