Biophysics

Distinct Activation Mechanisms of CXCR4 and ACKR3 Revealed by Single-Molecule Analysis of their Conformational Landscapes

1. Christopher T Schafer
2. Raymond F Pauszek
3. Martin Gustavsson
4. Tracy M Handel
5. David P Millar

• Curated by eLife

  eLife Assessment

  This manuscript describes the characterization of the conformational dynamics of two chemokine receptors at the single-molecule level using FRET. The authors make a convincing case for attributing the distinct interaction and pharmacology of the two receptors to differences in their conformational energy landscape. These important findings will be of interest to scientists working on activation mechanisms of GPCRs and signal transduction.

Reviewed by eLife

Elucidating the Mechanism Underlying UBA7•UBE2L6 Disulfide Complex Formation

1. Pei-Tzu Chen
2. Jia-Yin Yeh
3. Jui-Hsia Weng
4. Kuen-Phon Wu

• Curated by eLife

  eLife Assessment

  In this important study, the authors employed state-of-the-art biochemistry, cryo-EM, and HDX mass spec approaches to study the formation of the binary Uba7-UBE2L6 and ternary UBA7-UBE2L6-ISG15 complexes. The results established mechanisms by which UBA7 and UBE2L6 form disulfide bonds, disrupting the ISG15 transfer cascade. While the biochemical and structural experiments are largely convincing, the mechanism under in vivo conditions remains unclear, due to the limited use of a single E2 enzyme. The authors need to repeat their experiments with a representative panel of human E2 enzymes.

Reviewed by eLife

Coral anthozoan-specific opsins employ a novel chloride counterion for spectral tuning

1. Yusuke Sakai
2. Saumik Sen
3. Tomohiro Sugihara
4. Yukiya Kakeyama
5. Makoto Iwasaki
6. Gebhard FX Schertler
7. Xavier Deupi
8. Mitsumasa Koyanagi
9. Akihisa Terakita

• Curated by eLife

  eLife Assessment

  This study makes the fundamental discovery of the first natural animal rhodopsin that uses a chloride ion instead of an amino acid side chain as a counterion. Using a combination of biochemical and spectroscopic experiments together with QM/MM simulations, the authors identify the spectral tuning mechanism in the dark state and in the photoproduct state. The methods are sound and the results are convincing. This work will be of interest to biologists working on visual proteins and it also raises new questions about how environmental factors might affect coral opsins.

Reviewed by eLife

Progressive chromosome shape changes quantified during cell divisions

1. Yasutaka Kakui
2. Yoshiharu Kusano
3. Tereza Clarence
4. Maya Lopez
5. Toru Hirota
6. Bhavin S. Khatri
7. Frank Uhlmann

Reviewed by Review Commons

The C-terminus of the multi-drug efflux pump EmrE prevents proton leak by gating transport

1. Merissa Brousseau
2. Da Teng
3. Nathan E Thomas
4. Gregory A Voth
5. Katherine A Henzler-Wildman

• Curated by eLife

  eLife Assessment

  This fundamental study provides a comprehensive analysis of the EmrE efflux pump and the role of the C-terminal domain in preventing uncoupled proton leak in the absence of substrate. The evidence supporting the conclusions is solid, although incomplete analyses limit some of the conclusions.

Reviewed by eLife

Polyphosphate Discriminates Protein Conformational Ensembles More Efficiently than DNA Promoting Diverse Assembly and Maturation Behaviors

1. Saloni Goyal
2. Divya Rajendran
3. Anup Kumar Mani
4. Athi N Naganathan

• Curated by eLife

  eLife Assessment

  This manuscript offers important insights into how polyphosphate (polyP) influences protein phase separation differently from DNA. The authors present compelling evidence that polyP distinguishes between protein conformational states, leading to diverse condensate behaviors. However, differences in charge density between polyP and DNA complicate direct comparisons, and the extent to which polyP-driven phase transitions reveal initial protein states remains unclear. Addressing these concerns would strengthen the manuscript's impact for researchers interested in biomolecular condensates, protein dynamics, and stress response mechanisms.

Reviewed by eLife

Longitudinal Awake Imaging of Mouse Deep Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy

1. Yike Wang
2. Matthew R Lowerison
3. Zhe Huang
4. Qi You
5. Bing-Ze Lin
6. Daniel A Llano
7. Pengfei Song

• Curated by eLife

  eLife Assessment

  This study presents important methodologies for repeated brain ultrasound localization microscopy (ULM) in awake mice and a set of results indicating that wakefulness reduces vascularity and blood flow velocity. The data supporting these findings are solid. This study is relevant for scientists investigating vascular physiology in the brain.

Reviewed by eLife

Crossover in Aromatic Amino Acid Interaction Strength: Tyrosine vs. Phenylalanine in Biomolecular Condensates

1. David De Sancho
2. Xabier López

• Curated by eLife

  eLife Assessment

  This important study uses advanced computational methods to elucidate how environmental dielectric properties influence the interaction strengths of tyrosine and phenylalanine in biomolecular condensates. The evidence supporting the claims of the authors is solid, as the simulations are performed rigorously providing mechanistic insights into the origin of the differences between the two aromatic amino acids considered. This study will be of broad interest to researchers studying biomolecular phase separation.

Reviewed by eLife

Structural mechanisms of PIP ₂ activation and SEA0400 inhibition in human cardiac sodium-calcium exchanger NCX1

1. Jing Xue
2. Weizhong Zeng
3. Scott John
4. Nicole Attiq
5. Michela Ottolia
6. Youxing Jiang

• Curated by eLife

  eLife Assessment

  NCX1 is an important cardiac Ca2+/Na+ exchanger whose activity is tightly regulated. This manuscript describes the structural basis of activation by the lipid PIP2 and inhibition by binding of a small molecule to NCX1. These results provide key insights into NCX1 regulation and cellular Ca2+ signaling, but the evidence presented is still incomplete.

Reviewed by eLife

A differentiable Gillespie algorithm for simulating chemical kinetics, parameter estimation, and designing synthetic biological circuits

1. Krishna Rijal
2. Pankaj Mehta

• Curated by eLife

  eLife Assessment

  This important study introduces a fully differentiable variant of the Gillespie algorithm as an approximate stochastic simulation scheme for complex chemical reaction networks, allowing kinetic parameters to be inferred from empirical measurements of network outputs using gradient descent. The concept and algorithm design are convincing and innovative. While the proofs of concept are promising, some questions are left open about implications for more complex systems that cannot be addressed by existing methods. This work has the potential to be of significant interest to a broad audience of quantitative and synthetic biologists.

Reviewed by eLife