Biochemistry

Rac1 selectively binds a specific lamellipodin isoform via a noncanonical helical interface

1. Tong Gao
2. Pingfeng Zhang
3. Alison M. Kurimchak
4. James S. Duncan
5. Jinhua Wu

Reviewed by Arcadia Science

The temperature dependence of binding entropy is a selective pressure in protein evolution

1. Rosemary Georgelin
2. Hannah Bott
3. Joe A. Kaczmarski
4. Rebecca Frkic
5. Li Lynn Tan
6. Nobuhiko Tokuriki
7. Matthew A. Spence
8. Colin J. Jackson

Reviewed by PREreview

Categorizing prediction modes within low-pLDDT regions of AlphaFold2 structures

1. Christopher J Williams
2. Vincent B Chen
3. David C Richardson
4. Jane S Richardson

Reviewed by Arcadia Science

Phage-displayed synthetic library and screening platform for nanobody discovery

1. Baolong Xia
2. Ah-Ram Kim
3. Feimei Liu
4. Myeonghoon Han
5. Emily Stoneburner
6. Stephanie Makdissi
7. Francesca Di Cara
8. Stephanie E Mohr
9. Aaron Ring
10. Norbert Perrimon

• Curated by eLife

  eLife Assessment

  This important study presents an alternative platform for nanobody discovery using phage-displayed synthetic libraries. The evidence supporting the platform, which is used to isolate and validate nanobodies targeting Drosophila secreted proteins, is compelling. By making the library openly accessible, this provides an excellent resource to the wider scientific community. The paper presents a detailed protocol for nanobody screening; as this protocol is refined and optimized over time, this will increase the success rate for discovering nanobodies with improved properties using this alternative platform.

Reviewed by eLife

Elevated ubiquitin phosphorylation by PINK1 contributes to proteasomal impairment and promotes neurodegeneration

1. Cong Chen
2. Tong-Yao Gao
3. Hua-Wei Yi
4. Yi Zhang
5. Tong Wang
6. Zhi-Ling Lou
7. Tao-Feng Wei
8. Yun-Bi Lu
9. Tingting Li
10. Chun Tang
11. Wei-Ping Zhang

• Curated by eLife

  eLife Assessment

  This study provides important insights into the role of polyUbiquitination in neurodegenerative diseases, elucidating how pUb promotes neurodegeneration by affecting proteasomal function. The findings not only offer a new perspective on the pathophysiology of neurodegenerative diseases but also provide potential targets for developing new therapeutic strategies. The results provide solid evidence to support the conclusions.

Reviewed by eLife

Conformational dynamics and asymmetry in multimodal inhibition of membrane-bound pyrophosphatases

1. Jianing Liu
2. Anokhi Shah
3. Xinyu Liu
4. Joshua L Wort
5. Yue Ma
6. Katie Hardman
7. Niklas G Johansson
8. Orquidea Ribeiro
9. Adam Brookfield
10. Alice Bowen
11. Jari Yli-Kauhaluoma
12. Henri Xhaard
13. Lars JC Jeuken
14. Adrian Goldman
15. Christos Pliotas
16. Keni Vidilaseris

• Curated by eLife

  eLife Assessment

  This important study uncovers the mechanism of inhibition of a membrane pyrophosphatase by non-hydrolyzable phosphonate substrate analogs. Convincing crystallography, EPR spectroscopy, and functional measurements support the presence of a distinct conformational equilibrium of TmPPase in solution, and further supports the notion of asymmetric inhibitor binding at the active site, while maintaining a symmetric conformation at the periplasmic interface.

Reviewed by eLife

Mapping cryptic phosphorylation sites in the human proteome

1. Dino Gasparotto
2. Annarita Zanon
3. Valerio Bonaldo
4. Elisa Marchiori
5. Massimo Casagranda
6. Erika Di Domenico
7. Laura Copat
8. Tommaso Fortunato Asquini
9. Marta Rigoli
10. Sirio Vittorio Feltrin
11. Nuria Lopez Lorenzo
12. Graziano Lolli
13. Maria Pennuto
14. Jesùs R Requena
15. Omar Rota Stabelli
16. Giovanni Minervini
17. Cristian Micheletti
18. Giovanni Spagnolli
19. Pietro Faccioli
20. Emiliano Biasini

Reviewed by Review Commons

Structural insights into heterohexameric assembly of epilepsy-related ligand–receptor complex LGI1–ADAM22

1. Takayuki Yamaguchi
2. Kei Okatsu
3. Masato Kubota
4. Ayuka Mitsumori
5. Atsushi Yamagata
6. Yuko Fukata
7. Masaki Fukata
8. Mikihiro Shibata
9. Shuya Fukai

• Curated by eLife

  eLife Assessment

  In this convincing work by Yamaguchi et al. the cryo-EM structure of the heterohexameric 3:3 LGI1-ADAM22 complex is presented. The findings suggest that LGI1 can cluster ADAM22 in a trimeric fashion. The clustering of cell surface proteins is important in controlling signaling in the nervous system. This new version of the manuscript has been improved substantially and the figures have been enhanced and clarified.

Reviewed by eLife

A broad-spectrum antibiotic targets multiple-drug-resistant bacteria with dual binding targets and no detectable resistance

1. Wenyan He
2. Xueting Huan
3. Yinchuan Li
4. Qisen Deng
5. Tao Chen
6. Wen Xiao
7. Yijun Chen
8. Lingman Ma
9. Nan Liu
10. Zhuo Shang
11. Zongqiang Wang

Reviewed by Rapid Reviews Infectious Diseases

Dual-specific autophosphorylation of kinase IKK2 enables phosphorylation of substrate IκBα through a phosphoenzyme intermediate

1. Prateeka Borar
2. Tapan Biswas
3. Ankur Chaudhuri
4. Pallavi T Rao
5. Swasti Raychaudhuri
6. Tom Huxford
7. Saikat Chakrabarti
8. Gourisankar Ghosh
9. Smarajit Polley

• Curated by eLife

  eLife Assessment

  This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. The findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.

Reviewed by eLife