Biochemistry

Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase

1. Roberto Efraín Díaz
2. Andrew K Ecker
3. Galen J Correy
4. Pooja Asthana
5. Iris D Young
6. Bryan Faust
7. Michael C Thompson
8. Ian B Seiple
9. Steven Van Dyken
10. Richard M Locksley
11. James S Fraser

• Curated by eLife

  eLife assessment

  This structural and biochemical study of the mouse homolog of acidic mammalian chitinase (AMCase) enhances our understanding of the pH-dependent activity and catalytic properties of mouse AMCase, and it sheds light on its adaptation to different physiological pH environments. The methods and analysis of data are solid, providing several lines of evidence to support the development of mechanistic hypotheses. While the findings and interpretation will be valuable to those studying AMCase in mice, the broader significance, including extension of the results to other species including human, remain less clear.

Reviewed by eLife

Prominin 1 and Tweety Homology 1 both induce extracellular vesicle formation

1. Tristan A Bell
2. Bridget E Luce
3. Pusparanee Hakim
4. Virly Y Ananda
5. Hiba Dardari
6. Tran H Nguyen
7. Arezu Monshizadeh
8. Luke H Chao

Reviewed by Review Commons

The folding-limited nucleation of curli hints at an evolved safety mechanism for functional amyloid production

1. Jolyon K. Claridge
2. Chloe Martens
3. Brajabandhu Pradhan
4. Frank Sobott
5. Mike Sleutel
6. Han Remaut

Reviewed by Biophysics Colab

Structural analysis of the dynamic ribosome-translocon complex

1. Aaron JO Lewis
2. Frank Zhong
3. Robert J Keenan
4. Ramanujan S Hegde

• Curated by eLife

  eLife assessment

  This landmark work by Lewis and Hegde represents the most significant breakthrough in membrane and secretory biogenesis in recent years. Their work reveals with outstanding clarity how nascent transmembrane segments can pass through the gate of Sec61 into the ER membrane through the coordinated motions of a conformationally and compositionally dynamic machine. Among many other insights, the authors discovered how a new factor, RAMP4, contributes to the formation and function of the lateral gate for certain substrates. The technical quality of the work is exceptional, setting the bar appropriately high.

Reviewed by eLife

Structural and dynamic changes in P-Rex1 upon activation by PIP3 and inhibition by IP4

1. Sandeep K Ravala
2. Sendi Rafael Adame-Garcia
3. Sheng Li
4. Chun-Liang Chen
5. Michael A Cianfrocco
6. J Silvio Gutkind
7. Jennifer N Cash
8. John JG Tesmer

• Curated by eLife

  eLife assessment

  This important study contributes insights into the regulatory mechanisms of a protein governing cell migration at the membrane. The integration of approaches revealing protein structure and dynamics provides convincing data for a model of regulation and suggests a new allosteric role for a solubilized phospholipid headgroup. The work will be interesting to researchers focusing on signaling mechanisms, cell motility, and cancer metathesis.

Reviewed by eLife

Targeting protein-ligand neosurfaces using a generalizable deep learning approach

1. Anthony Marchand
2. Stephen Buckley
3. Arne Schneuing
4. Martin Pacesa
5. Pablo Gainza
6. Evgenia Elizarova
7. Rebecca M. Neeser
8. Pao-Wan Lee
9. Luc Reymond
10. Maddalena Elia
11. Leo Scheller
12. Sandrine Georgeon
13. Joseph Schmidt
14. Philippe Schwaller
15. Sebastian J. Maerkl
16. Michael Bronstein
17. Bruno E. Correia

Reviewed by PREreview

ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6-specific nanobody restricts M. tuberculosis growth in macrophages

1. Timothy A Bates
2. Mila Trank-Greene
3. Xammy Huu Wrynla
4. Aidan Anastas
5. Sintayehu K Gurmessa
6. Ilaria R Merutka
7. Shandee D Dixon
8. Anthony Shumate
9. Abigail R Groncki
10. Matthew AH Parson
11. Jessica R Ingram
12. Eric Barklis
13. John E Burke
14. Ujwal Shinde
15. Hidde L Ploegh
16. Fikadu G Tafesse

• Curated by eLife

  eLife assessment

  This useful study investigates two secreted Mycobacterium tuberculosis proteins, ESAT-6 and CFP10, using biochemical assays, including a Biolayer Interferometry assay. Solid experimental evidence demonstrates that ESAT-6 forms a tight interaction with CFP10 as a heterodimer at neutral pH and that ESAT-6 also forms a homodimer at acidic pH. Additional, more definitive evidence is required to describe how these proteins disrupt the phagosomal membrane. While improved compared to a previous version, the revised manuscript did not address these concerns adequately.

Reviewed by eLife

Mutational profiling of SARS-CoV-2 papain-like protease reveals requirements for function, structure, and drug escape

1. Xinyu Wu
2. Margareta Go
3. Julie V. Nguyen
4. Nathan W. Kuchel
5. Bernadine G. C. Lu
6. Kathleen Zeglinski
7. Kym N. Lowes
8. Dale J. Calleja
9. Jeffrey P. Mitchell
10. Guillaume Lessene
11. David Komander
12. Matthew E. Call
13. Melissa J. Call

Reviewed by PREreview

Stoichiometric 14-3-3ζ binding promotes phospho-Tau microtubule dissociation and reduces aggregation and condensation

1. Janine Hochmair
2. Maxime C. M. van den Oetelaar
3. Leandre Ravatt
4. Lisa Diez
5. Lenne J. M. Lemmens
6. Renata Ponce-Lina
7. Rithika Sankar
8. Maximilian Franck
9. Gesa Nolte
10. Ekaterina Semenova
11. Satabdee Mohapatra
12. Christian Ottmann
13. Luc Brunsveld
14. Susanne Wegmann

Reviewed by preLights

7,8-Dihydroxyflavone is a direct inhibitor of human and murine pyridoxal phosphatase

1. Marian Brenner
2. Christoph Zink
3. Linda Witzinger
4. Angelika Keller
5. Kerstin Hadamek
6. Sebastian Bothe
7. Martin Neuenschwander
8. Carmen Villmann
9. Jens Peter von Kries
10. Hermann Schindelin
11. Elisabeth Jeanclos
12. Antje Gohla

• Curated by eLife

  eLife assessment

  Following small molecule screens, this study provides convincing evidence that 7,8 dihydroxyflavone (DHF) is a competitive inhibitor of pyridoxal phosphatase. These results are important since they offer an alternative mechanism for the effects of 7,8 dihdroxyflavone in cognitive improvement in several mouse models. This paper is also significant due to the interest in the phosphatases and neurodegeneration fields.

Reviewed by eLife