Article
Biochemistry & Molecular Biology
Jun-ichi Kashiwakura, Nao Koizumi, Kodai Saitoh, Kota Kagohashi, Yuto Sasaki, Fuki Kobayashi, Shoya Kawahara, Yukie Yamauchi, Yuichi Kitai, Ryuta Muromoto, Kenji Oritani, Tadashi Matsuda
Summary: STAP-2 is an essential adaptor protein involved in regulating mast cell activation, particularly in response to IL-33 stimulation. Its deficiency leads to decreased cytokine production and impaired TLR4-mediated mast cell activation. The direct binding of STAP-2 to IKKα enhances NF-kappa B activity, contributing to the activation of mast cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Ganga B. Vamisetti, Abhishek Saha, Yichao J. Huang, Rajeshwer Vanjari, Guy Mann, Julia Gutbrod, Nabieh Ayoub, Hiroaki Suga, Ashraf Brik
Summary: By using the RaPID method and chemical protein synthesis, this study discovered a specific binder that can selectively inhibit protein-protein interactions associated with Lys63-linked Di-Ub. This discovery offers potential opportunities in modulating central Ub pathways and drug discovery areas associated with Ub signaling.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Moses M. Kasembeli, Efiyenia Kaparos, Uddalak Bharadwaj, Ahmad Allaw, Alain Khouri, Bianca Acot, David J. Tweardy
Summary: STAT3 mutations in the DNA-binding domain and Src-homology 2 domain have been found to cause immunodeficiency, malignancy, and autoimmunity. The study reveals that these mutations affect the stability of STAT3 monomer and homodimer, as well as its activation processes. Specifically, mutations in the DNA-binding domain result in reduced DNA binding, while mutations in the Src-homology 2 domain lead to increased DNA binding. Furthermore, mutations related to immunodeficiency show decreased conformational stability, affecting various activation events. Interventions targeting these mutations may have therapeutic potential.
Review
Biochemistry & Molecular Biology
Jun-ichi Kashiwakura, Kenji Oritani, Tadashi Matsuda
Summary: Adaptor molecules play a crucial role in signal transduction in immune cells and are potential therapeutic targets for T cell-mediated immune disorders. STAP-2, a member of the STAP family, is involved in T cell activation and autoimmune diseases. Understanding the impact of STAP-2 on T cell-mediated inflammation and immune diseases can aid in the development of novel therapeutic strategies.
Article
Cell Biology
Jessica J. A. Hummel, Casper C. Hoogenraad
Summary: In this study, the authors systematically investigated the selectivity and regulation of KIF1A-driven transport of different types of vesicles, emphasizing the importance of phosphorylation for vesicle binding and the role of specific adaptors in achieving cargo specificity. They propose a model where motor dimerization, posttranslational modifications, and specific adaptors regulate selective KIF1A cargo trafficking.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yuto Sasaki, Kodai Saitoh, Kota Kagohashi, Yuichi Kitai, Ryuta Muromoto, Kenji Oritani, Jun-Ichi Kashiwakura, Tadashi Matsuda
Summary: The study found that STAP-2 plays a significant role in the pathogenesis of autoimmune hepatitis by regulating the expression of FasL and the production of IFN-gamma, leading to increased liver necrosis and lymphocyte infiltration in STAP-2 KO mice compared to WT mice after ConA injection.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)
Article
Multidisciplinary Sciences
Rhiannon Morris, Yaoyuan Zhang, Julia Ellyard, Carola G. Vinuesa, James M. Murphy, Artem Laktyushin, Nadia J. Kershaw, Jeffrey J. Babon
Summary: The researchers presented structures of the substrate recognition (SH2) domain of LNK in complex with phosphorylated motifs from JAK2 and EPOR, providing insight into its binding specificity and mode of action.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Antonio Rodriguez-Blazquez, Arturo Carabias, Alba Moran-Vaquero, Sergio de Cima, Juan R. Luque-Ortega, Carlos Alfonso, Peter Schuck, Jose Antonio Manso, Sandra Macedo-Ribeiro, Carmen Guerrero, Jose M. de Pereda
Summary: C3G activation is regulated by phosphorylation and interaction with Crk adaptor proteins, revealing a two-factor mechanism for tight control of its activity.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Andrea Bernardini, Mariangela Lorenzo, Antonio Chaves-Sanjuan, Paolo Swuec, Matteo Pigni, Dana Saad, Petr V. Konarev, Melissa Ann Graewert, Erica Valentini, Dmitri I. Svergun, Marco Nardini, Roberto Mantovani, Nerina Gnesutta
Summary: NF-Y cooperates with USF1 in DNA binding and jointly activates target promoters. Certain unstructured domains adapt to small variations in stereo-alignments of TF sites.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Jesper Levring, Daniel S. Terry, Zeliha Kilic, Gabriel Fitzgerald, Scott Blanchard, Jue Chen
Summary: The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates salt and fluid homeostasis across epithelial membranes. Alterations in CFTR cause cystic fibrosis, a fatal disease without a cure. In this study, the authors investigate the structure and function of CFTR, specifically focusing on the dimerization of its nucleotide-binding domains (NBDs) and the allosteric gating mechanism that regulates chloride conductance. They also explore the effects of disease-causing substitutions on NBD dimerization and propose implications for potential clinical therapies.
Article
Chemistry, Multidisciplinary
Marta Falcicchio, Jake A. Ward, Sara Y. Chothia, Jaswir Basran, Alisha Mohindra, Salvador Macip, Pietro Roversi, Richard G. Doveston
Summary: 14-3-3 proteins play important roles in cellular processes and are implicated in cancer pathways. The covalent modification of 14-3-3 sigma by WR-1065, in combination with fusicoccin A, leads to enhanced efficacy in inducing cell death and attenuating cell growth in cancer cell lines, showing a novel therapeutic strategy.
Article
Multidisciplinary Sciences
David S. White, Sandipan Chowdhury, Vinay Idikuda, Ruohan Zhang, Scott T. Retterer, Randall H. Goldsmith, Baron Chanda
Summary: Research has shown both positive and negative cooperativity in cAMP binding, with limited parameter resolution in bulk measurements. By using nanophotonic zero-mode waveguides, individual ligand binding dynamics to multimeric ion channels have been directly resolved, revealing different kinetics in cAMP binding and isomerization. This approach can provide insights into binding allostery at single-molecule resolution in other intact membrane proteins and receptors.
Article
Hematology
Hongxia Fu, Yan Jiang, Wesley P. Wong, Timothy A. Springer
Summary: Von Willebrand factor (VWF) is an important ultra-long concatemeric protein in hemostasis and thrombosis. Self-association of VWF molecules in flow is reversible and has a self-limiting mechanism. The tension in tethered VWF plays a crucial role in mediating association between VWF molecules.
Article
Multidisciplinary Sciences
Daehun Park, Yumei Wu, Sang-Eun Lee, Goeun Kim, Seonyoung Jeong, Dragomir Milovanovic, Pietro De Camilli, Sunghoe Chang
Summary: The combination of synapsin and synaptophysin proteins in fibroblasts efficiently reconstitutes synaptic vesicle clusters with similar morphology and liquid-like properties to those found at synapses, suggesting they play a key role in the assembly of synaptic structures.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Atsunori Kaneshige, Longchuan Bai, Mi Wang, Donna McEachern, Jennifer L. Meagher, Renqi Xu, Paul D. Kirchhoff, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Shaomeng Wang
Summary: We discovered a potent and selective STAT5 degrader with strong antitumor activity in vivo. Using PROTAC technology, we transformed small-molecule ligands into selective STAT5 degraders, with AK-2292 as the best compound. AK-2292 effectively induced degradation of STAT5 proteins in AML cell lines and showed strong antitumor activity in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Elizabeth A. Caselle, Jennifer H. Yoon, Sagar Bhattacharya, Joel J. L. Rempillo, Zsofia Lengyel, Areetha D'Souza, Yurii S. Moroz, Patricia L. Tolbert, Alexander N. Volkov, Marcello Forconi, Carlos A. Castaneda, Olga V. Makhlynets, Ivan V. Korendovych
Article
Chemistry, Physical
Yiran Yang, Holly B. Jones, Thuy P. Dao, Carlos A. Castaneda
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Biochemistry & Molecular Biology
Thuy P. Dao, Brian Martyniak, Ashley J. Canning, Yongna Lei, Erica G. Colicino, Michael S. Cosgrove, Heidi Hehnly, Carlos A. Castaneda
Editorial Material
Multidisciplinary Sciences
Jennifer Cable, Clifford Brangwynne, Geraldine Seydoux, David Cowburn, Rohit V. Pappu, Carlos A. Castaneda, Luke E. Berchowitz, Zhijuan Chen, Martin Jonikas, Abby Dernburg, Tanja Mittag, Nicolas L. Fawzi
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2019)
Article
Multidisciplinary Sciences
Minh-Ha Nguyen, Marie Martin, Henry Kim, Frank Gabel, Olivier Walker, Maggy Hologne
SCIENTIFIC REPORTS
(2019)
Article
Chemistry, Physical
Moreno Marcellini, Minh-Ha Nguyen, Marie Martin, Maggy Hologne, Olivier Walker
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Review
Biochemistry & Molecular Biology
Thuy P. Dao, Carlos A. Castaneda
Article
Biology
Kevin E. W. Namitz, Tongyin Zheng, Ashley J. Canning, Nilda L. Alicea-Velazquez, Carlos A. Castaneda, Michael S. Cosgrove, Steven D. Hanes
Summary: Researchers identified a bivalent interaction between yeast Ess1 and CTD peptides of RNA polymerase II, suggesting an anchored mechanism of isomerization. The study raised the possibility of eukaryotic parvulin-class prolyl isomerases gaining broader substrate specificity during evolution by acquiring a flexible linker for a more dynamic binding mode.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Julia F. Riley, Peter J. Fioramonti, Amber K. Rusnock, Heidi Hehnly, Carlos A. Castaneda
Summary: The study reveals that ALS-related mutations in UBQLN2 gene affect the assembly and material properties of stress-induced UBQLN2 condensates, with mutant UBQLN2 forming fewer and smaller condensates compared to wild-type UBQLN2. Different mutations have varying effects on condensate properties, highlighting the position- and amino acid-dependent impact of ALS-linked mutations.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tongyin Zheng, Sarasi K. K. Galagedera, Carlos A. Castaneda
Summary: The shuttle protein UBQLN2 functions in protein quality control by binding to proteasomal receptors and ubiquitinated substrates through its UBL and UBA domains, respectively. The interplay between the folded domains and intrinsically disordered regions mediates liquid-liquid phase separation of UBQLN2. The interactions between UBL and UBA domains, as well as disordered regions, are crucial for understanding the phase behavior and physiological functions of UBQLN2.
Article
Multidisciplinary Sciences
Tingting Niu, Charlotte De Rosny, Severine Chautard, Amaury Rey, Danish Patoli, Marine Groslambert, Camille Cosson, Brice Lagrange, Zhirong Zhang, Orane Visvikis, Sabine Hacot, Maggy Hologne, Olivier Walker, Jeimin Wong, Ping Wang, Romeo Ricci, Thomas Henry, Laurent Boyer, Virginie Petrilli, Benedicte F. Py
Summary: Activation of Nlrp3 inflammasome requires recruitment of Nek7 for ASC speck formation. The phosphorylation status of NLRP3 S803 controls this recruitment, playing a crucial role in inflammasome assembly. These findings suggest that targeting NLRP3 S803 phosphorylation may be a potential strategy for controlling inflammasome-related inflammatory responses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Thuy P. Dao, Yiran Yang, Maria F. Presti, Michael S. Cosgrove, Jesse B. Hopkins, Weikang Ma, Stewart N. Loh, Carlos A. Castaneda
Summary: This study reveals that the effects of multivalent polyubiquitin chains on UBQLN2 LLPS depend on the chain types. Chains with extended conformations promote UBQLN2 LLPS, while chains that inhibit LLPS have different conformations. These findings provide insights into how polyubiquitin chains interact with and regulate proteins.
Article
Chemistry, Physical
Yoan Monneau, Cyrielle Arrault, Coraline Duroux, Marie Martin, Fabien Chirot, Luke Mac Aleese, Marion Girod, Clothilde Comby-Zerbino, Agnes Hagege, Olivier Walker, Maggy Hologne
Summary: Silver has been used as an antimicrobial agent, but some Gram-negative bacteria have developed resistance, leading to deaths in burn units. The protein SilE plays a crucial role in bacterial silver resistance. Through various techniques, it has been found that SilE consists of four helical segments and has four strong silver binding sites. These findings enhance our understanding of the mechanism of SilE in the silver efflux pump complex and aid in the development of inhibitors to combat bacterial silver resistance.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Lucille Babel, Minh-Ha Nguyen, Cedric Mittelheisser, Marie Martin, Katharina M. Fromm, Olivier Walker, Maggy Hologne
Summary: The study demonstrates the role of SilE in storing silver ions and proposes for the first time the interplay between SilB and SilE through experiments using model peptides and techniques such as NMR and CD.
CHEMICAL COMMUNICATIONS
(2021)
Meeting Abstract
Biophysics
Po-Chia Chen, Maggy Hologne, Olivier Walker, Janosch Hennig
BIOPHYSICAL JOURNAL
(2020)