Biophysics

Multivalency, autoinhibition, and protein disorder in the regulation of interactions of dynein intermediate chain with dynactin and the nuclear distribution protein

1. Kayla A Jara
2. Nikolaus M Loening
3. Patrick N Reardon
4. Zhen Yu
5. Prajna Woonnimani
6. Coban Brooks
7. Cat H Vesely
8. Elisar J Barbar

• Curated by eLife

  Evaluation Summary:

  The identification of an autoinhibitory mechanism of the dynein intermediate chain provides an important contribution to our understanding of dynein assembly and illustrates the plethora of regulatory mechanisms attainable by intrinsically disordered proteins. This paper provides insight into the autoinhibited inactive state of dynein as well as the activation mechanism. A wide range of biophysical approaches is used, providing a very nice example of how these diverse technologies can be applied in concert and in a synergistic manner to study an important question in the realm of "unstructured biology".

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Recovering mixtures of fast-diffusing states from short single-particle trajectories

1. Alec Heckert
2. Liza Dahal
3. Robert Tjian
4. Xavier Darzacq

• Curated by eLife

  Evaluation Summary:

  The authors describe new approaches to improve the analysis of single-molecule tracking data to uncover multiple diffusive states of proteins in living cells. This paper will be of interest to researches from the fields of experimental biology, who are interested in tracking of proteins using microscopy, as well as computational scientists who are interested in devising novel methodologies for analysis of multiple-particle tracking data. The paper presents two advanced techniques for estimation of motion parameters (such as diffusion coefficients) and contains rigorous evaluation using simulated and real biological data.

  (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

Ear pinnae in a neotropical katydid (Orthoptera: Tettigoniidae) function as ultrasound guides for bat detection

1. Christian A Pulver
2. Emine Celiker
3. Charlie Woodrow
4. Inga Geipel
5. Carl D Soulsbury
6. Darron A Cullen
7. Stephen M Rogers
8. Daniel Veitch
9. Fernando Montealegre-Z

• Curated by eLife

  Evaluation Summary:

  Remarkably, Katydids, insects related to grasshoppers and crickets, have ears in their left and right forelegs. Pulver and colleagues show convincingly how two specialized chambers lining the hearing organs function as sound resonators that effectively boost the perception of high ultrasonic frequencies. This enables Katydids to detect the echolocating pulses of their bat predators before they home in on them for a meal. This study uses an impressive combination of approaches, but the manuscript would be improved by greater clarity.

  (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

Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery

1. Dmitry Shvarev
2. Jannis Schoppe
3. Caroline König
4. Angela Perz
5. Nadia Füllbrunn
6. Stephan Kiontke
7. Lars Langemeyer
8. Dovile Januliene
9. Kilian Schnelle
10. Daniel Kümmel
11. Florian Fröhlich
12. Arne Moeller
13. Christian Ungermann

• Curated by eLife

  Evaluation Summary:

  This manuscript reports the cryo-EM structure of HOPS, a heterohexameric tether that participates in the fusion of late endosomes, autophagosomes, and AP-3 vesicles with lysosomes. The structure will be of interest to a wide range of cell biologists and structural biologists who study membrane traffic. However, while the structural data are elegant, the functional interpretations need further support.

  (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

Automated systematic evaluation of cryo-EM specimens with SmartScope

1. Jonathan Bouvette
2. Qinwen Huang
3. Amanda A Riccio
4. William C Copeland
5. Alberto Bartesaghi
6. Mario J Borgnia

• Curated by eLife

  Evaluation Summary:

  Bouvette et al. describe a new software for fully automated cryo-EM sample screening and data acquisition, making use of deep-learning-based algorithms for the detection of regions and objects of interest. This is the first example of software for fully automated grid screening, which is of great interest to the cryo-EM community, to free skilled researchers and engineers from a serious of tedious tasks, so that they can devote more time to method development or finding answers to interesting biological and medical questions.

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

Reviewed by eLife

The kinetic landscape of human transcription factors

1. Nicholas E Mamrak
2. Nader Alerasool
3. Daniel Griffith
4. Alex S Holehouse
5. Mikko Taipale
6. Timothée Lionnet

Reviewed by ASAPbio crowd review

Mechanism of the cadherin–catenin F-actin catch bond interaction

1. Amy Wang
2. Alexander R Dunn
3. William I Weis

• Curated by eLife

  Evaluation Summary:

  This work investigated the mechanism of the cadherin-catenin F-actin catch bond interaction, a fundamental cell-cell adhesive structure that can be both dynamic and force-activated. Force measurements with purified protein components demonstrate that the catch bond results from a force-dependent switch of the actin-binding domain of αE-catenin between a five-helix bundle and a four-helix bundle bound on F-actin. The findings are interesting and well supported by experimental data, and will be interesting to the broader field of cytoskeleton function and functional structural biology.

  (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

Computational exploration of treadmilling and protrusion growth observed in fire ant rafts

1. Robert J. Wagner
2. Franck J. Vernerey

• Curated by eLife

  Evaluation Summary:

  In this study, the authors present a numerical model of ant raft shape dynamics. It is an interesting topic, the experimental movies are exciting, and the idea that ant rafts make protrusions is new. The goal seems to be to explain how local interactions can lead to the perpetual protrusions of the raft. Since the biological significance of the results has not been clarified, the paper is likely to be primarily interesting to engineers and experts on robotics.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Dynamic allostery in substrate binding by human thymidylate synthase

1. Jeffrey P Bonin
2. Paul J Sapienza
3. Andrew L Lee

• Curated by eLife

  Evaluation Summary:

  The authors analyze the mechanisms of entropically driven cooperativity in the human thymidylate synthase (hTS), an enzyme essential for DNA replication and a promising target for anticancer drugs. The authors conclude that the cooperative binding of dUMP ligands to its two identical sites arises from a disproportionate reduction in the enzyme's conformational entropy upon binding the first ligand. The results provide rare insights into the mechanisms of ligand binding for an essential human protein and should be of great interest to readers interested in enzyme structure/dynamics/function relationships, cooperativity and allostery, and possible drug targeting of thymidylate synthase.

  (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

Threonine phosphorylation regulates the molecular assembly and signaling of EGFR in cooperation with membrane lipids

1. Ryo Maeda
2. Hiroko Tamagaki-Asahina
3. Takeshi Sato
4. Masataka Yanagawa
5. Yasushi Sako

Reviewed by Review Commons