Biophysics

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

Myristoyl’s dual role in allosterically regulating and localizing Abl kinase

1. Svenja de Buhr
2. Frauke Gräter

• Curated by eLife

  eLife assessment

  This is an important study of the mechanism of how binding of the fatty acid myristic acid (MYR) inhibits the activity of the kinase c-Abl, a critical regulator of many cellular processes. While the general aspects of this regulation are known from structure determination and biochemical studies, the exact molecular mechanism and the nature of the allosteric inhibition were not known. The authors use MD simulation to close this gap and provide a detailed mechanistic description of the inhibitory mechanism, although some of the evidence remains incomplete.

Reviewed by eLife

Intracellular Helix-Loop-Helix Domain Modulates Inactivation Kinetics of Mammalian TRPV5 and TRPV6 Channels

1. Lisandra Flores-Aldama
2. Daniel Bustos
3. Deny Cabezas-Bratesco
4. Wendy Gonzalez
5. Sebastian E. Brauchi

• Curated by Biophysics Colab

  Evaluation statement (1 September 2023)

  Flores-Aldama and colleagues set out to identify molecular determinants of fast inactivation in the TRPV6 ion channel, a mechanism not observed in the closely related TRPV5 channel. The work focuses on a helix-loop-helix (HLH) motif, located at the interface between several important regions for channel gating. Using molecular dynamics simulations and analysis of mutations, the authors identify pairs of amino acid residues in a structural triad formed by the HLH, S2-S3 linker, and transmembrane domains, which show different conformations in the available TRPV5 and TRPV6 cryo-EM structures. An important aspect of the study is that some of the structural hypotheses were derived from an evolutionary analysis of sequences from orthologues of both channels, demonstrating the value of this type of analysis.

  Biophysics Colab considers this to be a convincing study and recommends it to scientists interested in the molecular determinants of ion channel gating.

  (This evaluation 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