Article
Chemistry, Physical
Konstantin Roder
Summary: The study explores the potential and free energy landscape of histone tails, revealing a set of distinct structural ensembles crucial for the formation of liquid-like chromatin organization. The presence of multiple structures on a multifunnel energy landscape may be associated with multifunctionality.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Cell Biology
Meghan T. Harris, Michael T. Marr II
Summary: Cells activate stress response pathways to survive adverse conditions by inhibiting global translation and utilizing alternative methods of translation initiation, such as IRES. Cellular IRESs have been identified in many stress response transcripts. eIF5B promotes IRES activity through its N-terminal region via a non-canonical mechanism.
Article
Biochemistry & Molecular Biology
Morgan A. Gingerich, Jie Zhu, Biaoxin Chai, Michael P. Vincent, Nuli Xie, Vaibhav Sidarala, Nicholas A. Kotov, Debashish Sahu, Daniel J. Klionsky, Santiago Schnell, Scott A. Soleimanpour
Summary: CLEC16A is an E3 ubiquitin ligase that plays a crucial role in regulating mitochondrial quality control through mitophagy and is associated with various human diseases. A recent study discovered an internal intrinsically disordered protein region (IDPR) within CLEC16A that is essential for its function and turnover. This IDPR is targeted by RNF41 to promote CLEC16A degradation and destabilize the CLEC16A-RNF41-USP8 complex. These findings highlight the importance of the IDPR in controlling the regulatory balance between CLEC16A and RNF41, which could be therapeutically targeted to improve mitochondrial health in disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biology
Sandhya Balasubramanian, Matteo Andreani, Julia Goncalves Andrade, Tannishtha Saha, Devakumar Sundaravinayagam, Javier Garzon, Wenzhu Zhang, Oliver Popp, Shin-ichiro Hiraga, Ali Rahjouei, Daniel B. Rosen, Philipp Mertins, Brian T. Chait, Anne D. Donaldson, Michela Di Virgilio
Summary: RIF1 is a multifunctional protein involved in DNA repair and replication, and its phosphorylation is crucial for protecting nascent DNA from degradation.
Article
Cell Biology
Xiao Han, Zixin Hu, Wahyu Surya, Qianqian Ma, Feng Zhou, Lars Nordenskiold, Jaume Torres, Lanyuan Lu, Yansong Miao
Summary: The IDR region in the coronin family plays a critical role in optimizing the biochemical activities of coronins, both in vivo and in vitro, by fine-tuning oligomerization and maintaining proper protein structure.
Article
Biochemistry & Molecular Biology
Emilie Aponte, Marie Lafitte, Audrey Sirvent, Valerie Simon, Maud Barbery, Elise Fourgous, Mariano Maffei, Florence Armand, Romain Hamelin, Julie Pannequin, Philippe Fort, Miquel Pons, Serge Roche, Yvan Boublik
Summary: This study reveals the important role of the unique domain ULBR in Src tyrosine kinase in malignant cell transformation. The ULBR is involved in membrane anchoring, MAPK signaling, and phosphorylation of specific membrane-localized tyrosine kinases needed for Src oncogenic signaling.
Article
Biochemistry & Molecular Biology
Katarzyna Soltys, Krzysztof Wycisk, Andrzej Ozyhar
Summary: The study focused on the liquid-liquid phase separation properties of the AB region of human RXR gamma receptor, highlighting the importance of hydrophobic interactions in the formation of liquid condensates.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Isabel M. Martin, Camilo Aponte-Santamaria, Lisa Schmidt, Marius Hedtfeld, Adel Iusupov, Andrea Musacchio, Frauke Graeter
Summary: The central intrinsically disordered region (IDR) of the inner centromere protein (INCENP) undergoes conformational changes upon phosphorylation, leading to expansion of the IDR. The transition between globule and coil conformations of the IDR is non-monotonic and dependent on the degree of phosphorylation. Phosphorylation regulates the cohesiveness and phase behavior of INCENP IDR assemblies, influencing the function of INCENP in chromosome segregation.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Goro Kato
Summary: This review discusses the structural and functional aspects of Src protein and its regulatory mechanism. By reviewing nuclear magnetic resonance analyses and recent studies, the authors explore new characteristics and regulatory roles of Src protein. Finally, the new regulatory roles are integrated with the canonical model to elucidate the functions of full-length Src.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Katarzyna Soltys, Andrzej Ozyhar
Summary: RXR beta is a subtype of human retinoid X receptor (RXR) that is expressed in almost all tissues. It has a unique and longest N-terminal sequence called the AB region, which exhibits ligand-independent activation function. The molecular properties of the AB region of RXR beta (AB_hRXRB) have been characterized through biochemical and biophysical analysis, along with in silico examinations. AB_hRXRB displays characteristics of a coil-like intrinsically disordered region and can undergo liquid-liquid phase separation (LLPS), similar to another subtype of RXR - RXR gamma (AB_hRXRG).
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Mao Zhang, Cheng Zhu, Yuanyuan Duan, Tongbao Liu, Haoping Liu, Chang Su, Yang Lu
Summary: A unique group of PP2C phosphatases from fungi and plants have been found to sense CO2, but not HCO3-, to control diverse cellular programmes. They have intrinsically disordered regions (IDR) that form reversible liquid-like droplets through phase separation and are activated in response to elevated environmental CO2 in an IDR-dependent manner.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emery T. Usher, Nafiseh Sabri, Roman Rohac, Amie K. Boal, Tanja Mittag, Scott A. Showalter
Summary: The interaction between Pdx1 and SPOP causes SPOP relocalization from nuclear speckles to the diffuse nucleoplasm, where the ubiquitination activity of Pdx1 mediated by SPOP occurs. Efficient turnover of Pdx1 requires both SB motifs. The subnuclear localization of SPOP-substrate interactions and substrate ubiquitination may be directed by the properties of the substrate itself.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Marta Vicioso-Mantis, Raquel Fueyo, Claudia Navarro, Sara Cruz-Molina, Wilfred F. J. van Ijcken, Elena Rebollo, Alvaro Rada-Iglesias, Marian A. Martinez-Balbas
Summary: This study uncovers the essential role of the coactivator JMJD3 in the assembly and gene activation of enhancer-clusters. The involvement of the intrinsically disordered region in JMJD3 in the formation of biomolecular condensates is demonstrated using live-cell imaging techniques. These findings shed light on the relationship between the 3D-conformation of chromatin and the TGF beta-driven response during mammalian neurogenesis.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Guanlan Fan, Fan Wang, Yurou Chen, Qian Zheng, Jie Xiong, Qiongying Lv, Kejia Wu, Jiaqiang Xiong, Lei Wei, Dongqing Li, Jiachen Zhang, Wei Zhang, Feng Li
Summary: In this study, OTUD1 is identified as an Akt-associated protein and is downregulated upon Akt activation. Ectopic OTUD1 inhibits Akt phosphorylation, and a short peptide (OUN-36) located in the OTUD1 N-terminal intrinsically disordered region strongly binds to the Akt PH domain. OUN-36-based therapy efficiently abrogates Akt feedback reactivation and sensitizes cancer cells to chemotherapy and immunotherapy.
Article
Cell Biology
Morgan A. Gingerich, Xueying Liu, Biaoxin Chai, Gemma L. Pearson, Michael P. Vincent, Tracy Stromer, Jie Zhu, Vaibhav Sidarala, Aaron Renberg, Debashish Sahu, Daniel J. Klionsky, Santiago Schnell, Scott A. Soleimanpour
Summary: CLEC16A regulates mitochondrial health through mitophagy and is associated with over 20 human diseases. This study reveals the importance of a C-terminal intrinsically disordered protein region (IDPR) in CLEC16A for mitochondrial quality control. The stability of CLEC16A is dependent on proline bias within the C-terminal IDPR.
Article
Genetics & Heredity
Simona Ghenea, Marioara Chiritoiu, Robi Tacutu, Antonio Miranda-Vizuete, Stefana Maria Petrescu
Summary: This study investigates the role of EDEM proteins in ER stress response and reveals that they have a broader function than previously recognized. The findings provide insights into the regulation of ER stress and have implications for clinical and therapeutic investigations.
Article
Multidisciplinary Sciences
Gabriela N. Chiritoiu, Marioara Chiritoiu, Cristian V. A. Munteanu
Summary: This research focuses on the role of EDEM2 in protein selection and degradation, utilizing various proteomics techniques to identify associated proteins and potential substrates. The study verified the findings through biochemical experiments and validated datasets published in Molecular and Cellular Proteomics.
Article
Pharmacology & Pharmacy
Sorina Andreea Anghel, Rodica Aura Badea, Gabriela Chiritoiu, David Sebastian Patriche, Petruta Ramona Alexandru, Florentina Pena
Summary: GLP-1 secretion plays a crucial role in controlling blood glucose levels. A newly developed cell line allowed for rapid assessment of GLP-1 secretion. The discovery of quercetin as a potent GLP-1 secretagogue opens up possibilities for developing alternative glucose-lowering therapies.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Iulia-Roxana Angelescu, Silvia-Simona Grosu-Tudor, Lucia-Roxana Cojoc, Gabriel-Mihai Maria, Gabriela N. Chiritoiu, Cristian V. A. Munteanu, Medana Zamfir
Summary: Traditional fermented foods in Romania can provide a rich source of novel lactic acid bacteria with functional properties, such as Lactobacillus helveticus 34.9, which has the ability to inhibit the growth of various bacteria and produce a large bacteriocin. The production of the bacteriocin is enhanced under stress conditions and its mode of action and degree of inhibition depend on the concentration and indicator strain used. The bacteriocin treatment induces morphological changes in sensitive strains, making it a potential candidate for applications in health, food, and non-food related fields.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2022)
Article
Plant Sciences
Eliza C. Martin, Laurentiu Spiridon, Aska Goverse, Andrei-Jose Petrescu
Summary: An examination of over 80,000 plant Nod-like receptors (NLRs) revealed a diverse sequence underlying functional specificity. Conserved sequence motifs were identified using machine learning techniques. NLRexpress, a software package, was developed to efficiently detect these motifs and enable screening of proteomes, transcriptomes, or genomes.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Plant Sciences
Irene Louise van Grinsven, Eliza C. Martin, Andrei-Jose Petrescu, Richard Kormelink
Summary: Plant disease immunity relies on the recognition of pathogens and immune pathway activation. Nod-like receptors, such as Tsw, play a crucial role in this process. Tsw, a Nod-like resistance gene with unusually large LRR domains, confers resistance against TSWV. However, the function of the majority of the LRR structure remains unclear.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eliza C. Martin, Catalin F. Ion, Florin Ifrimescu, Laurentiu Spiridon, Jaap Bakker, Aska Goverse, Andrei-J Petrescu
Summary: NLRscape is a webserver that hosts a collection of over 80,000 plant protein sequences and provides various tools for exploring the complex sequence landscape of this class of proteins. Users can analyze the distribution of NLR family sequence features in the plant kingdom using different analytical tools.
NUCLEIC ACIDS RESEARCH
(2023)
Editorial Material
Cell Biology
Marioara Chiritoiu-Butnaru, Sarah E. E. Stewart, Min Zhang, Vivek Malhotra, Julien Villeneuve
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Cristian V. A. Munteanu, Gabriela N. N. Chiritoiu, Andrei-Jose Petrescu, Stefana M. Petrescu
Summary: N-glycosylation is a crucial process in various biological functions, and class I mannosidases play an important role in the early protein sorting and quality control. In this study, we investigated the oligomannosidic glycoprotein load and characterized the early secretory pathway (ESP) in melanoma cells using a custom workflow combining glycomics and deglycoproteomics analyses. We found that the majority of ESP are involved in cell communication via extracellular matrix, particularly integrin-mediated communication, and adopt Man9 N-glycans in cells with inhibited class I mannosidase activity. Furthermore, we observed decreased core-fucosylation following inhibition of class I mannosidases, which could be explained by reduced FUT8 protein levels.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Nicolas Papadopoulos, Audrey Nedelec, Allison Derenne, Teodor Asvadur Sulea, Christian Pecquet, Ilyas Chachoua, Gaelle Vertenoeil, Thomas Tilmant, Andrei-Jose Petrescu, Gabriel Mazzucchelli, Bogdan I. Iorga, Didier Vertommen, Stefan N. Constantinescu
Summary: In myeloproliferative neoplasms, frameshift mutants of calreticulin turn into rogue cytokines by inducing constitutive activation of the Thrombopoietin Receptor (TpoR). Here, the authors define how mutant calreticulin acquires specificity for TpoR binding and triggers its constitutive activation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Roxana-Olimpia Gheorghe, Andreea Violeta Grosu, Melania Magercu, Mihail-Sebastian Ghenghea, Cristina Elena Zbarcea, Alexandra Tanase, Simona Negres, Alexandru Filippi, Gabriela Chiritoiu, Mihaela Gherghiceanu, Sorina Dinescu, Gisela Gaina, Damir Sapunar, Violeta Ristoiu
Summary: In the early stages after traumatic nerve injury, resident macrophages in the dorsal root ganglia play a crucial role in the development of neuropathic pain. By interacting with the cytoskeleton, these macrophages can be transformed into an anti-inflammatory phenotype, leading to a reduction in neuropathic pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Petruta R. (Flintoaca) Alexandru, Gabriela N. Chiritoiu, Daniela Lixandru, Sabina Zurac, Constantin Ionescu-Targoviste, Stefana M. Petrescu
Summary: Pancreatic beta cells produce and secrete insulin in response to rises in blood glucose. This study identifies EDEM1 as a new regulator of insulin synthesis and secretion, and proposes it as a potential target for diabetes treatment. EDEM1 inhibits the IRE1/JNK/c-Jun pathway, leading to increased insulin mRNA levels and secretion.