Article
Biochemistry & Molecular Biology
Andrea Eisenreichova, Evzen Boura
Summary: This article reports the crystal structure of the complex formed by SARS-CoV-2 nucleocapsid protein and 14-3-3 protein, revealing the details of the binding. The study found that the N protein forms a complex with 14-3-3 protein through phosphorylation, and the central binding groove of 14-3-3 protein plays a key role. These findings enhance our understanding of the viral infection mechanism.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Bente A. Somsen, Fenna W. B. Craenmehr, Wei-Hong W. Liu, Auke A. Koops, Marloes A. M. Pennings, Emira J. Visser, Christian Ottmann, Peter J. Cossar, Luc Brunsveld
Summary: Molecular glues represent a novel approach in drug discovery, however, the targeted stabilization of protein complexes is still challenging due to a lack of drug design rules. This study demonstrates the successful development of a peptide-based molecular glue that selectively stabilizes the 14-3-3/ChREBP protein-protein interaction by utilizing the functional mapping of hotspots.
Article
Biology
Pavel Pohl, Rohit Joshi, Olivia Petrvalska, Tomas Obsil, Veronika Obsilova
Summary: The study investigated the structural basis of Nedd4-2 regulation by 14-3-3 and identified phosphorylated Ser342 and Ser448 as key residues facilitating 14-3-3 binding. The Nedd4-2:14-3-3 complex induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dhruv C. Rathod, Sonali M. Vaidya, Marie-T. Hopp, Toni Kuehl, Diana Imhof
Summary: Heme plays a dual role in biological processes, functioning as a prosthetic group of hemoproteins and also regulating biochemical pathways through transient association with proteins. However, the mechanisms of heme recognition and complex formation with target proteins are poorly understood. This report focuses on evaluating mammalian heme-regulated proteins and their heme-binding motifs (HBMs), particularly the Cys-Pro dipeptide motifs. This analysis provides insights into the sequence and structural anomalies observed during transient heme binding and protein regulation.
Article
Biochemistry & Molecular Biology
Guennadi Kozlov, Sandy Mattijssen, Jianning Jiang, Samuel Nyandwi, Tara Sprules, James R. Iben, Steven L. Coon, Sergei Gaidamakov, Anne M. Noronha, Christopher J. Wilds, Richard J. Maraia, Kalle Gehring
Summary: In this study, the La-module of LARP1 was characterized, and it was found that unlike other LARPs, the La-module of LARP1 does not contain an RRM domain. The La-module alone is capable of binding poly(A) RNA with high specificity for the RNA 3'-end. This study provides insights into the functional relevance of LARP1 RNA binding in cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Claire C. Munier, Christian Ottmann, Matthew W. D. Perry
Summary: The 14-3-3 proteins play crucial roles in regulating the inflammatory response at genetic, molecular, and cellular levels. They affect key components of the immune response and can lead to clinical syndromes when their recognition processes are disrupted. Abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Xavier Guillory, Inesa Hadrovic, Pim J. de Vink, Andrea Sowislok, Luc Brunsveld, Thomas Schrader, Christian Ottmann
Summary: The rational design of protein-protein interaction (PPI) inhibitors presents a challenge, but a novel approach combining a general supramolecular protein binder with a specific peptidic ligand has resulted in a strong PPI inhibitor with significantly increased protein affinity. X-ray crystal structure elucidation and Molecular Dynamics (MD) simulations have provided unique molecular insights into the binding mode of this inhibitor, opening up new avenues for studying PPIs with novel chemical tools.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Fisheries
Xiaoyi Pan, Qiang Gao, Jinyu Shen, Ting Xu
Summary: This study identified Mr14-3-3 as a binding protein for MrTV-VP3, playing a crucial role in MrTV infection and potentially serving as a target for anti-MrTV therapies.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kristina Tugaeva, Andrey A. Sysoev, Anna A. Kapitonova, Jake L. R. Smith, Phillip Zhu, Richard B. Cooley, Alfred A. Antson, Nikolai N. Sluchanko
Summary: Phosphorylation of SARS-CoV-2 nucleoprotein recruits human cytosolic 14-3-3 proteins that play a role in virus replication. Using genetic code expansion, it is shown that 14-3-3 binding is triggered by phosphorylation at specific sites on the nucleoprotein. Crystal structures and biochemical data reveal that 14-3-3 binding obstructs a region of the nucleoprotein and inhibits its dephosphorylation. The strength of the 14-3-3/nucleoprotein interaction may be linked to the replicative fitness of the virus.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lea Reuter, Tanja Schmidt, Prabha Manishankar, Christian Throm, Jutta Keicher, Andrea Bock, Irina Droste-Borel, Claudia Oecking
Summary: NPH3 plays a crucial role in auxin-dependent plant phototropism, with blue light triggering its dissociation from the plasma membrane through phosphorylation and interaction with 14-3-3 proteins. In darkness, NPH3 binds polyacidic phospholipids for membrane association. The dynamic change in NPH3 localization mediated by 14-3-3 is essential for auxin-dependent phototropism.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
S. Grace Herod, Annie Dyatel, Stefanie Hodapp, Marko Jovanovic, Luke E. Berchowitz
Summary: Amyloids play important roles in age-related diseases. Some cells use reversible amyloid-like structures for translational control. Yeast 14-3-3 proteins bind to amyloid-like assemblies and facilitate their clearance, contributing to global protein aggregate homeostasis. These findings suggest that 14-3-3 proteins may protect against pathological protein aggregates.
Article
Multidisciplinary Sciences
Gergo Gogl, Kristina V. Tugaeva, Pascal Eberling, Camille Kostmann, Gilles Trave, Nikolai N. Sluchanko
Summary: The 14-3-3 proteins can recognize phosphorylated motifs within various protein partners, and display different affinities when binding to E6 oncoproteins, but follow a conserved affinity ranking. This knowledge allows predicting the proportions of 14-3-3 isoforms engaged with phosphoproteins in different tissues.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Anna A. Kapitonova, Kristina V. Tugaeva, Larisa A. Varfolomeeva, Konstantin M. Boyko, Richard B. Cooley, Nikolai N. Sluchanko
Summary: Nucleophosmin 1 (NPM1) is a multifunctional protein that regulates ribosome biogenesis, centrosome duplication, and chromatin remodeling. Recent studies have shown the importance of the phosphorylation site Ser48 in the interaction of NPM1 with other proteins, including 14-3-3. The crystal structure analysis reveals the binding mode between 14-3-3 protein and phosphopeptide.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Dmitri Segal, Stefan Maier, Giovanni J. Mastromarco, Wesley Wei Qian, Syed Nabeel-Shah, Hyunmin Lee, Gaelen Moore, Jessica Lacoste, Brett Larsen, Zhen-Yuan Lin, Abeeshan Selvabaskaran, Karen Liu, Craig Smibert, Zhaolei Zhang, Jack Greenblatt, Jian Peng, Hyun O. Lee, Anne-Claude Gingras, Mikko Taipale
Summary: This study maps the interactomes of all human 14-3-3 paralogs and characterizes their effect on client protein localization. It reveals that 14-3-3 proteins function as chaperone-like molecules and negatively regulate the localization and activity of certain proteins. These findings reshape our understanding of the function of 14-3-3 proteins.
Article
Biochemistry & Molecular Biology
Sarah A. Bennison, Sara M. Blazejewski, Xiaonan Liu, Gal Hacohen-Kleiman, Shlomo Sragovich, Sofia Zoidou, Olga Touloumi, Nikolaos Grigoriadis, Illana Gozes, Kazuhito Toyo-oka
Summary: Defective neuritogenesis is a contributing mechanism in neurodevelopmental disorders, particularly in ADNP syndrome. Adnp is localized to the cytoplasm by binding with 14-3-3 proteins, and its knockdown inhibits neurite formation. Adnp deficiency leads to morphological and functional abnormalities in the cortex, including increased dendrite number and axon length.
MOLECULAR PSYCHIATRY
(2023)