Biophysics

Approximating Projections of Conformational Boltzmann Distributions with AlphaFold2 Predictions: Opportunities and Limitations

1. Benjamin P. Brown
2. Richard A. Stein
3. Jens Meiler
4. Hassane S. Mchaourab

Reviewed by PREreview

Allosteric regulation of kinase activity in living cells

1. Shivani Sujay Godbole
2. Nikolay V Dokholyan

• Curated by eLife

  eLife assessment

  One of the most promising strategies in development of drugs targeting kinases is provided by using allosteric control that allows specific regulation and study of kinase function without directly targeting the active site. This important paper reviews convincingly the current repertoire of tools for regulating the activity of protein kinases with the ultimate goal of developing novel approaches in treating diseases associated with signal dysregulation.

Reviewed by eLife

Conformational heterogeneity of the BTK PHTH domain drives multiple regulatory states

1. David Yin-wei Lin
2. Lauren E Kueffer
3. Puneet Juneja
4. Thomas E Wales
5. John R Engen
6. Amy H Andreotti

• Curated by eLife

  eLife assessment

  BTK, a TEC-family tyrosine kinase activated by the B-cell antigen receptor, contains a variety of regulatory domains and it is subject to complex regulation by membrane phospholipids, protein ligands, phosphorylation, and dimerization. This study presents convincing evidence, utilizing various biophysical techniques, to support a model for BTK activation that will be valuable for the field. Overall, the study enhances the understanding of BTK's activation mechanism, autoinhibition, and allosteric control, challenging previous assumptions about BTK.

Reviewed by eLife

Short disordered termini and proline-rich domain are major regulators of UBQLN1/2/4 phase separation

1. Thuy P. Dao
2. Anitha Rajendran
3. Sarasi K.K. Galagedera
4. William Haws
5. Carlos A. Castañeda

Reviewed by preLights

An Ultrasensitive Genetically Encoded Voltage Indicator Uncovers the Electrical Activity of Non‐Excitable Cells

1. Philipp Rühl
2. Anagha G. Nair
3. Namrata Gawande
4. Sassrika N. C. W. Dehiwalage
5. Lukas Münster
6. Roland Schönherr
7. Stefan H. Heinemann

Reviewed by Arcadia Science

Autoinhibited kinesin-1 adopts a hierarchical folding pattern

1. Zhenyu Tan
2. Yang Yue
3. Felipe Leprevost
4. Sarah Haynes
5. Venkatesha Basrur
6. Alexey I Nesvizhskii
7. Kristen J Verhey
8. Michael A Cianfrocco

• Curated by eLife

  eLife assessment

  This paper will be of significant interest to the research community working on cytoplasmic transport and microtubule motors, offering important insights into the structural arrangement of autoinhibited Kinesin-1. The paper reports a structural model of full-length kinesin-1 describing its autoinhibitory mechanism using cryo-EM, Alphafold structural predictions, cross-linking, and mass spectrometry. The data are of high quality and together offer a compelling model for how Kinesin-1 is autoinhibited, indicating that auto-inhibition does not rely on the IAK motif alone but on a more extensive intramolecular interface.

Reviewed by eLife

Single-shot quantitative phase imaging with polarization differential interference contrast

1. Mark Strassberg
2. Yana Shevtsova
3. Domenick Kamel
4. Kai Wagoner-Oshima
5. Hualin Zhong
6. Min Xu

Reviewed by Arcadia Science

Ultrastructural insights into the microsporidian infection apparatus reveal the kinetics and morphological transitions of polar tube and cargo during host cell invasion

1. Himanshu Sharma
2. Nathan Jespersen
3. Kai Ehrenbolger
4. Lars-Anders Carlson
5. Jonas Barandun

Reviewed by Review Commons

Ligand bias underlies differential signaling of multiple FGFs via FGFR1

1. Kelly Karl
2. Nuala Del Piccolo
3. Taylor Light
4. Tanaya Roy
5. Pooja Dudeja
6. Vlad-Constantin Ursachi
7. Bohumil Fafilek
8. Pavel Krejci
9. Kalina Hristova

• Curated by eLife

  eLife assessment

  This manuscript describes useful data on the mechanisms underlying the activation of the receptor tyrosine kinase FGFR1 and stimulation of intracellular signaling pathways in response to FGF4, FGF8, or FGF9 binding to the extracellular domain of FGFR1. Solid evidence for quantitative differences in the downstream responses induced by the three ligands is presented. This manuscript will be of interest to biochemists and cell biologists working on receptor tyrosine kinases and general cell signalling across membranes.

Reviewed by eLife

Glutamate helps unmask the differences in driving forces for phase separation versus clustering of FET family proteins in sub-saturated solutions

1. Mrityunjoy Kar
2. Laura T. Vogel
3. Gaurav Chauhan
4. Hannes Ausserwöger
5. Timothy J. Welsh
6. Anjana R. Kamath
7. Tuomas P. J. Knowles
8. Anthony A. Hyman
9. Claus A. M. Seidel
10. Rohit V. Pappu

Reviewed by preLights