Biophysics

Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with Pol α - Primase

1. Mairi L. Kilkenny
2. Charlotte E. Veale
3. Amir Guppy
4. Steven W. Hardwick
5. Dimitri Y. Chirgadze
6. Neil J. Rzechorzek
7. Joseph D. Maman
8. Luca Pellegrini

Reviewed by ScreenIT

Homo-oligomerization of the human adenosine A2A receptor is driven by the intrinsically disordered C-terminus

1. Khanh Dinh Quoc Nguyen
2. Michael Vigers
3. Eric Sefah
4. Susanna Seppälä
5. Jennifer Paige Hoover
6. Nicole Star Schonenbach
7. Blake Mertz
8. Michelle Ann O'Malley
9. Songi Han

• Curated by eLife

  Evaluation Summary:

  The work will be of interest to anyone interested in signal transduction, and especially those studying GPCRs and membrane receptors. Dimerization and oligomerization of G protein-coupled membrane receptors (GPCRs) are expected to be critical for receptor function. This intriguing study helps understand the usually underestimated role of GPCR soluble domains. The authors discovered that oligomerization of a GPCR can be mediated by multiple weak interactions between soluble domains that are "tunable" by environmental factors, thus possibly modulating the function of this important class of membrane receptor proteins. What remains to be shown is how oligomerization alters receptor function.

  (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 name with the authors.)

Reviewed by eLife

High-speed, three-dimensional imaging reveals chemotactic behaviour specific to human-infective Leishmania parasites

1. Rachel C Findlay
2. Mohamed Osman
3. Kirstin A Spence
4. Paul M Kaye
5. Pegine B Walrad
6. Laurence G Wilson

• Curated by eLife

  Evaluation Summary:

  This study utilizes holographic microscopy to study the swimming behaviour of flagellated forms of Leishmania mexicana in the presence or absence of host cell stimuli. Infective metacyclic promastigotes were found to swim faster than actively dividing procyclic promastigotes and to display different average trajectories. The swimming trajectories of these parasite stages were also altered in the presence of macrophages, promoting chemotaxis towards target host cells. The findings provide new insights into promastigote flagellar function and role of swimming behaviour in promoting pathogenesis.

  (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

Discovery and characterization of Hv1-type proton channels in reef-building corals

1. Gisela Rangel-Yescas
2. Cecilia Cervantes
3. Miguel A Cervantes-Rocha
4. Esteban Suárez-Delgado
5. Anastazia T Banaszak
6. Ernesto Maldonado
7. Ian Scott Ramsey
8. Tamara Rosenbaum
9. Leon D Islas

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest both to marine biologists and to biophysicists studying voltage-gated proton channels. It describes cloning and full biophysical characterization of the first ion channel ever identified in reef-building coral species, and develops a mechanistic model for understanding regulation of voltage-gated proton channels.

  (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

Persistent cell migration emerges from a coupling between protrusion dynamics and polarized trafficking

1. Kotryna Vaidžiulytė
2. Anne-Sophie Macé
3. Aude Battistella
4. William Beng
5. Kristine Schauer
6. Mathieu Coppey

• Curated by eLife

  Evaluation Summary:

  Cell movement is essential for development and tissue homeostasis. While the cellular machineries involved in movement have been well studied, how cells maintain a persistent direction of motion is less well understood. Here, Coppey's team shows that movement persistence emerges from the coupling of two cellular systems: protrusions at the leading edge and polarity of secretion. This coupling is controlled by the small GTPase Cdc42. The authors propose a physical model that recapitulates the coupling, defines two key parameters and explains persistent cell migration.

  (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

Cryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling

1. Monique S Straub
2. Carolina Alvadia
3. Marta Sawicka
4. Raimund Dutzler

• Curated by eLife

  Evaluation Summary:

  This paper reports the atomic structure of XKR9, a membrane protein that is implicated in initiating the process to get rid of cells that are undergoing programmed cell death (apoptosis). The protein of interest was originally proposed to be a lipid channel, but the work presented here suggests that it is unlikely to function in this capacity alone. As a first step in this nascent field, the paper should be of interest to membrane structural biologists, and those working on lipid transport and apoptosis.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Markov state models of proton- and pore-dependent activation in a pentameric ligand-gated ion channel

1. Cathrine Bergh
2. Stephanie A Heusser
3. Rebecca Howard
4. Erik Lindahl

• Curated by eLife

  Evaluation Summary:

  This article presents molecular dynamics simulations of the pH-gated pentameric ion channel GLIC, which has been the subject of many structural and functional studies. GLIC can be considered as a model system for pentameric ligand-gated ion channels that are responsible for fast chemical-electrical communication between cells in animals. The findings include the solution of open- and closed-like channel forms, intermediates and a "pre-desensitised" state. The approach reproduces modulation by pH and mutation, surprisingly finding a predominance of closed channels, despite activating conditions, and suggest a role for asymmetry in channel gating. Overall, the sampling of channel dynamics is significant and the description of state interconversions sheds new light on pLGIC mechanisms.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Allosteric Control of Structural Mimicry and Mutational Escape in the SARS-CoV-2 Spike Protein Complexes with the ACE2 Decoys and Miniprotein Inhibitors: A Network-Based Approach for Mutational Profiling of Binding and Signaling

1. Gennady M. Verkhivker
2. Steve Agajanian
3. Deniz Yasar Oztas
4. Grace Gupta

Reviewed by ScreenIT

Sequence of the SARS-CoV-2 spike transmembrane domain makes it inherently dynamic

1. Sahil Lall
2. Padmanabhan Balaram
3. M.K. Mathew
4. Shachi Gosavi

Reviewed by ScreenIT

SARS-CoV-2 Variants Are Selecting for Spike Protein Mutations That Increase Protein Stability

1. David Shorthouse
2. Benjamin A. Hall

Reviewed by preLights, ScreenIT