Biophysics

The prolactin receptor scaffolds Janus kinase 2 via co-structure formation with phosphoinositide-4,5-bisphosphate

1. Raul Araya-Secchi
2. Katrine Bugge
3. Pernille Seiffert
4. Amalie Petry
5. Gitte W Haxholm
6. Kresten Lindorff-Larsen
7. Stine Falsig Pedersen
8. Lise Arleth
9. Birthe B Kragelund

• Curated by eLife

  eLife assessment

  This important interdisciplinary study substantially advances our understanding of the prolactin receptor interactions with the membrane lipids and the effect of these interactions on cell signaling. The authors use a combination of state-of-the-art NMR structural analysis, simulations, and cellular assays to provide compelling experimental evidence for protein complexes being regulated by IDR-membrane interactions. The work will be of broad interest to structural biologists and biochemists, and the results presented herein are likely relevant for other non-tyrosine kinase receptors.

Reviewed by eLife

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization

1. Artur Ruppel
2. Dennis Wörthmüller
3. Vladimir Misiak
4. Manasi Kelkar
5. Irène Wang
6. Philippe Moreau
7. Adrien Méry
8. Jean Révilloud
9. Guillaume Charras
10. Giovanni Cappello
11. Thomas Boudou
12. Ulrich S Schwarz
13. Martial Balland

• Curated by eLife

  eLife assessment

  Using surface micropatterning, optical activation, and theoretical analysis, the authors provide compelling evidence that adjacent cells actively propagate mechanical stress in epithelial tissues. The response of the receiver cell is active and enhanced when the principal stress direction is perpendicular to the orientation of actin fibers. This work is important and a must-read for everybody wanting to understand tissue mechanics.

Reviewed by eLife

Regulation of chromatin microphase separation by binding of protein complexes

1. Omar Adame-Arana
2. Gaurav Bajpai
3. Dana Lorber
4. Talila Volk
5. Samuel Safran

• Curated by eLife

  eLife assessment

  This fundamental work substantially advances our understanding of polymer physics underpinnings of genome folding, organization, and regulation. The conclusions are supported by both convincing computer simulations and analytical theory. The work will be of significant interest to the genome folding community.

Reviewed by eLife

Structural and functional properties of the transporter SLC26A6 reveal mechanism of coupled anion exchange

1. David N Tippett
2. Colum Breen
3. Stephen J Butler
4. Marta Sawicka
5. Raimund Dutzler

• Curated by eLife

  eLife assessment

  This important manuscript combines cryo-EM and a suite of compelling whole cell and proteoliposome transport assays to establish the mechanism and structure of the full-length human SLC26A6 chloride/bicarbonate exchangers, including the first partial view of the previously unresolved IVS region of an SLC26 STAS domain. In combination with prior studies on additional SLC26 paralogs, including the SLC26A9 paralog initially reported by the same group, the study provides broadly relevant insights into the mechanistic diversity of the SLC26 transporters. This study is of interest to the biophysics community and the field of membrane transport.

Reviewed by eLife

Structural and functional properties of a plant NRAMP-related aluminum transporter

1. Karthik Ramanadane
2. Márton Liziczai
3. Dragana Markovic
4. Monique S Straub
5. Gian T Rosalen
6. Anto Udovcic
7. Raimund Dutzler
8. Cristina Manatschal

• Curated by eLife

  eLife assessment

  This study provides valuable insight into the diversity within the NRAMP superfamily of transporters. Evidence of divalent metal ion transport and the structure (obtained without added metal ions) are convincing. However, molecular insight into Al3+ recognition and transport is incomplete, and the work would be strengthened by the determination of a metal-bound structure or additional experiments (such as molecular dynamics simulations or quantitative Al3+ binding/transport assays) to support the proposed Al3+ binding site. The work will be of interest to structural biologists and biophysicists studying NRAMP transporters.

Reviewed by eLife

Zinc activation of OTOP proton channels identifies structural elements of the gating apparatus

1. Bochuan Teng
2. Joshua P Kaplan
3. Ziyu Liang
4. Kevin Saejin Chyung
5. Marcel P Goldschen-Ohm
6. Emily R Liman

• Curated by eLife

  eLife assessment

  This valuable study discovers that zinc ions can activate some OTOP proton channels, identifying a pharmacological tool for research, and further establishing that OTOP channels gate. The data presented provide convincing support for the conclusions made by the authors, and the study is expected to be of considerable interest to physiologists investigating OTOP and other proton channels.

Reviewed by eLife

A pH-dependent cluster of charges in a conserved cryptic pocket on flaviviral envelopes

1. Lorena Zuzic
2. Jan K Marzinek
3. Ganesh S Anand
4. Jim Warwicker
5. Peter J Bond

• Curated by eLife

  eLife assessment

  The study represents an impressive effort to use atomistic simulations to probe cryptic binding sites in the envelope of six flaviviruses. Moreover, using constant pH simulations, the authors suggest that a cluster of ionizable residues contribute to the pH dependent conformational rearrangements required in the infection process. Therefore, the study provides new mechanistic insights that can be helpful in future efforts to develop drugs that target flaviviruses.

Reviewed by eLife

PAR recognition by PARP1 regulates DNA‐dependent activities and independently stimulates catalytic activity of PARP1

1. Waghela Deeksha
2. Suman Abhishek
3. Eerappa Rajakumara

Reviewed by Review Commons

Room-temperature crystallography reveals altered binding of small-molecule fragments to PTP1B

1. Tamar Skaist Mehlman
2. Justin T Biel
3. Syeda Maryam Azeem
4. Elliot R Nelson
5. Sakib Hossain
6. Louise Dunnett
7. Neil G Paterson
8. Alice Douangamath
9. Romain Talon
10. Danny Axford
11. Helen Orins
12. Frank von Delft
13. Daniel A Keedy

• Curated by eLife

  eLife assessment

  Based on two room-temperature X-ray crystallographic screens of PTP1B phosphatase against two sets of chemical fragments, and by comparing the results from a previous cryo screen, the authors report the important observation that, in addition to overlapping but non-identical sets of hits compared to the cryo screen, the room-temperature screens lead to significant differences in terms of binding sites and poses for some of the hits. The study provides compelling support for the use of room-temperature X-ray crystallography in early-stage drug discovery and highlights that temperature should be used as a parameter in efforts to extract additional insight from such analyses.

Reviewed by eLife

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

1. Sean M Braet
2. Theresa SC Buckley
3. Varun Venkatakrishnan
4. Kim-Marie A Dam
5. Pamela J Bjorkman
6. Ganesh S Anand

• Curated by eLife

  eLife assessment

  This fundamental and timely study provides insights into the structural dynamics of several relevant mutant forms of SARS-CoV-2 spike protein, including the most recent omicron variant. The hydrogen/deuterium-exchange studies provide compelling evidence for the stabilization of the spike stalk in conjunction with increased dynamics of the N-terminal domain, where binding to the ACE2 receptor occurs. These results have profound implications for the development of small molecule inhibitors of the spike protein-ACE2 receptor interaction.

Reviewed by eLife